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[SQUEAKING]

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[RUSTLING]

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[CLICKING]

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MATTHEW VANDER HEIDEN:
So last time, we

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00:00:12,490 --> 00:00:14,860
discussed the TCA cycle.

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00:00:14,860 --> 00:00:18,830
And that allows us to
then, you know, say

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00:00:18,830 --> 00:00:22,420
how we can take glucose and
completely oxidize those six

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00:00:22,420 --> 00:00:24,430
glucose carbons into CO2.

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00:00:24,430 --> 00:00:27,250
And you know, of course,
glycolysis converts glucose

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00:00:27,250 --> 00:00:28,570
into two pyruvate.

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00:00:28,570 --> 00:00:31,720
Pyruvate has two carbons, and
then pyruvate dehydrogenase

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00:00:31,720 --> 00:00:35,845
can release the first
of those carbons as CO2.

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00:00:35,845 --> 00:00:37,420
It generates an acetyl CoA.

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00:00:37,420 --> 00:00:39,940
That acetyl CoA then
enters the TCA cycle,

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00:00:39,940 --> 00:00:43,300
and two other CO2s
are released--

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00:00:43,300 --> 00:00:45,110
one of the isocitrate
dehydrogenase

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00:00:45,110 --> 00:00:48,130
step, one of the alpha
ketoglutarate dehydrogenase

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00:00:48,130 --> 00:00:49,180
step.

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00:00:49,180 --> 00:00:51,520
Now, we discussed that
the TCA cycle is useful

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00:00:51,520 --> 00:00:54,370
because it allows you
to oxidize anything that

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00:00:54,370 --> 00:00:57,220
can be turned into
acetyl CoA into CO2,

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00:00:57,220 --> 00:00:59,530
and that includes
fatty acids, which

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00:00:59,530 --> 00:01:02,900
we will spend a lot of
time talking about today.

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00:01:02,900 --> 00:01:07,450
Now, the TCA cycle, as I
mentioned, just by review,

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00:01:07,450 --> 00:01:11,170
is also very useful as a
way to make stuff-- lots

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00:01:11,170 --> 00:01:12,550
of useful intermediates.

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00:01:12,550 --> 00:01:14,800
But we discussed last time
if we're going to do that--

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00:01:14,800 --> 00:01:17,140
that is, because it
functions as a cycle--

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00:01:17,140 --> 00:01:19,210
if we remove stuff
from the cycle,

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00:01:19,210 --> 00:01:22,390
something has to be added back
in-- so-called anaplerosis--

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00:01:22,390 --> 00:01:26,260
in order to have it continue
to function as a cycle.

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00:01:26,260 --> 00:01:28,810
Now, you'll note-- we
weren't explicit about this,

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00:01:28,810 --> 00:01:30,010
but this is oxidation.

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00:01:30,010 --> 00:01:32,710
Remember, carbon oxidation
is generally favorable.

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00:01:32,710 --> 00:01:35,650
So delta G of this
will be less than 0.

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00:01:35,650 --> 00:01:37,750
However, unlike
glycolysis, where

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00:01:37,750 --> 00:01:42,940
we discussed that most of
the harnessing of energy--

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00:01:42,940 --> 00:01:47,500
that is, the favorable oxidation
of glucose to pyruvate--

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00:01:47,500 --> 00:01:52,300
was captured to directly keep an
ATP/ADP ratio high in the cell,

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00:01:52,300 --> 00:01:56,110
you can see that most of the
energy output of the TCA cycle

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00:01:56,110 --> 00:02:00,340
isn't actually direct
synthesis of ATP or GTP.

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00:02:00,340 --> 00:02:03,250
Instead, what we have is
we have most of that energy

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00:02:03,250 --> 00:02:08,110
as being captured and charging
up a ratio of NADH to NAD,

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00:02:08,110 --> 00:02:10,330
or FADH2 to FAD.

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00:02:10,330 --> 00:02:12,280
And we'll see over the
next several lectures

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00:02:12,280 --> 00:02:16,270
how we can harness electron
transfer from those molecules

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00:02:16,270 --> 00:02:21,380
to oxygen to make ATP, as
well as do some other work.

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00:02:21,380 --> 00:02:23,650
But before we get
to that, I want

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00:02:23,650 --> 00:02:27,400
to first focus a
bit on fat, which,

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00:02:27,400 --> 00:02:31,280
of course, is the most reduced
carbon biomolecule in the cell.

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00:02:31,280 --> 00:02:39,550
And so that's chains of
fully reduced carbon.

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00:02:39,550 --> 00:02:42,280
And of course, this is the
most chemically dense way

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00:02:42,280 --> 00:02:43,770
to store energy--

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00:02:43,770 --> 00:02:45,400
as carbon.

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00:02:45,400 --> 00:02:48,770
Intuitively, you know this,
because what's oil and gas?

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00:02:48,770 --> 00:02:51,410
It's chains of
reduced hydrocarbons.

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00:02:51,410 --> 00:02:53,050
Of course, those
are better fuels

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00:02:53,050 --> 00:02:55,870
than wood, which are,
as we saw before,

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based on carbohydrate
alcohol carbons.

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00:03:01,060 --> 00:03:03,130
You also know
intuitively that fat

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has more calories than sugar--

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00:03:04,870 --> 00:03:07,390
exactly same ideas.

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00:03:07,390 --> 00:03:09,730
And so I want to
start by discussing

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00:03:09,730 --> 00:03:12,190
what biological fat
is, and then that

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00:03:12,190 --> 00:03:13,900
will lead into a
discussion about how

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00:03:13,900 --> 00:03:18,850
we can oxidize the fat,
also, as a way to get energy.

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00:03:18,850 --> 00:03:21,910
Now, most biological
fat is packaged

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00:03:21,910 --> 00:03:24,220
into molecules called lipids.

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00:03:24,220 --> 00:03:28,480
And so I want to make
clear that lipids are not

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00:03:28,480 --> 00:03:31,080
the same thing as fat.

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00:03:31,080 --> 00:03:36,090
More correctly, a lipid contains
fat-- or more precisely,

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00:03:36,090 --> 00:03:38,145
something called a fatty acid.

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00:03:40,990 --> 00:03:43,530
And so what is a fatty acid?

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00:03:43,530 --> 00:03:46,500
Well, it's this fully
saturated hydrocarbon

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00:03:46,500 --> 00:03:48,910
with a carboxylic
acid on the end.

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00:03:48,910 --> 00:03:54,330
And so we have a
carboxylic acid followed

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00:03:54,330 --> 00:04:02,020
by some chain of fully
saturated hydrocarbons.

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00:04:02,020 --> 00:04:04,410
So it differs from
oil and gasoline

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00:04:04,410 --> 00:04:09,460
in that it has this carboxylic
acid handle, if you will,

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00:04:09,460 --> 00:04:14,100
on the end that basically allows
biology to build and break down

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00:04:14,100 --> 00:04:17,680
these fatty acids.

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00:04:17,680 --> 00:04:25,200
Now, most biological fatty acids
have even numbers of carbons.

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00:04:25,200 --> 00:04:27,930
And it turns out that that's
a consequence of the fact

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00:04:27,930 --> 00:04:31,290
that it's built and broken
down into these two carbon

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00:04:31,290 --> 00:04:33,480
acetyl CoA units.

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00:04:33,480 --> 00:04:35,460
And the most common lengths--

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00:04:35,460 --> 00:04:38,670
that is, how long
these chains are.

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00:04:38,670 --> 00:04:43,770
So in biology, they can vary
anywhere from 4 to 36 carbons

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00:04:43,770 --> 00:04:44,430
long.

90
00:04:44,430 --> 00:04:48,180
But the most common ones
are 12 to 24 carbons,

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00:04:48,180 --> 00:04:53,730
with 16 carbons and 18 carbons
being by far the most abundant

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00:04:53,730 --> 00:04:55,140
in cells.

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00:04:55,140 --> 00:04:57,600
Now, it's worth
mentioning what some

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00:04:57,600 --> 00:05:00,270
of the names of these
more common ones are,

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00:05:00,270 --> 00:05:02,010
because you'll see them.

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00:05:02,010 --> 00:05:13,010
And so the fully saturated
16 carbon fatty acid--

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00:05:13,010 --> 00:05:15,160
so 16 carbon total.

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00:05:15,160 --> 00:05:19,790
14, 15, 16, including
the carboxylic acid.

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00:05:19,790 --> 00:05:23,830
This is referred
to as palmitate.

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00:05:23,830 --> 00:05:26,560
Or it's drawn in the
acid form, palmitic acid.

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00:05:26,560 --> 00:05:37,750
And the systematic name for
this is hexadecanoic acid.

102
00:05:37,750 --> 00:05:42,105
The other common one,
the 18 carbon version--

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00:05:45,000 --> 00:05:49,050
so same molecule, but
two carbons longer.

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00:05:49,050 --> 00:05:54,150
That's referred to as
stearate, or stearic acid,

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00:05:54,150 --> 00:05:55,830
if drawn in the acid form.

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00:05:55,830 --> 00:06:06,440
Or the systematic name
would be octadecanoic acid.

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00:06:06,440 --> 00:06:09,460
Now, oftentimes
things like palmitate

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00:06:09,460 --> 00:06:12,265
can also be drawn like this.

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00:06:23,470 --> 00:06:25,480
So there's 16 carbons.

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00:06:25,480 --> 00:06:27,540
Another way to draw palmitate.

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00:06:27,540 --> 00:06:30,540
And you'll note that
palmitate as well as stearate

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00:06:30,540 --> 00:06:33,210
here are fully saturated.

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00:06:36,460 --> 00:06:38,630
What do I mean by saturated?

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00:06:38,630 --> 00:06:41,920
I mean fully saturated
by electrons.

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00:06:41,920 --> 00:06:45,370
There's no way to reduce
this molecule further,

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00:06:45,370 --> 00:06:50,590
unless, of course, we reduce
the carboxylic acid on the end.

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00:06:50,590 --> 00:06:52,900
And so palmitate
would be the most

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00:06:52,900 --> 00:06:55,420
saturated 16 carbon fatty acid.

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00:06:55,420 --> 00:07:00,980
Stearate is the most saturated
18 carbon fatty acid.

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00:07:00,980 --> 00:07:08,760
Now, if I add a double bond
to one of these molecules,

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that's an oxidation.

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00:07:10,710 --> 00:07:13,080
So just like when we
added a double bond

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00:07:13,080 --> 00:07:16,380
to succinate to make
fumarate in the TCA cycle.

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00:07:16,380 --> 00:07:17,610
I showed that last time.

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00:07:17,610 --> 00:07:20,200
That's an oxidation reaction.

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00:07:20,200 --> 00:07:25,770
And so an unsaturated
fatty acid is

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00:07:25,770 --> 00:07:29,040
a fatty acid that is no longer
fully saturated with electrons.

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00:07:29,040 --> 00:07:31,350
That means it is
not fully reduced.

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00:07:31,350 --> 00:07:34,230
And so, remember, you store
energy as reduced carbon.

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00:07:34,230 --> 00:07:38,250
And so an unsaturated fatty
acid stores less energy

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00:07:38,250 --> 00:07:41,460
than a saturated fatty
acid because it's

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more oxidized than the
saturated fatty acid.

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00:07:45,460 --> 00:07:48,120
And so just as a couple
examples here-- so here's

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the example of a 16-carbon
unsaturated fatty acid.

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00:07:56,240 --> 00:07:58,560
So I introduce a double bond.

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I'll draw it in
the acid form here.

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And so here you got 5,
6, 7, 8 plus 7 is 15--

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16 carbons total,
one double bond.

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00:08:16,140 --> 00:08:27,150
This is all middle oleic acid,
more systematically named

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00:08:27,150 --> 00:08:35,370
hexadecene acid.

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00:08:35,370 --> 00:08:39,390
And the 18-carbon version
would be as follows.

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So I added two extra carbons
on this end of the molecule.

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This is oleic acid,
or octadecanoic acid.

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00:09:11,430 --> 00:09:15,160
Now, note I put a
double bond in here.

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00:09:15,160 --> 00:09:17,760
You'll remember from
organic chemistry

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that double bonds can exist
in a trans or a cis form.

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00:09:24,700 --> 00:09:32,130
And so if it's trans,
it would be like this.

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00:09:32,130 --> 00:09:42,080
If it's cis, the
double bond would be

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00:09:42,080 --> 00:09:45,530
like that in the carbon chain.

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And so just to show
you here on the models

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that this can matter, so here
is a double bonded carbon.

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And so these two red guys
are cis to each other.

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00:09:56,490 --> 00:09:59,390
And this purple
is trans to that.

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Now, if I put this onto
a fatty acid chain,

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00:10:03,110 --> 00:10:06,340
you can see that there's
a big difference there.

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00:10:06,340 --> 00:10:10,250
So if I add the
double bond in here

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and it's continued the
chain here on a trans bond,

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it's a relatively
straight molecule,

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whereas if I go
here in a cis bond,

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I now introduce a kink
into the alkyl chain.

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00:10:23,100 --> 00:10:29,000
So biological fatty
acids are always cis.

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And this is
structurally important

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because it actually creates
this kink in fatty acids

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that are not fully saturated.

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Now, obviously, as
you might guess,

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00:10:41,790 --> 00:10:43,940
the number of double
bonds and the locations

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00:10:43,940 --> 00:10:47,000
of the double bonds will change
the structure and therefore

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00:10:47,000 --> 00:10:49,380
the properties of
the fatty acids.

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00:10:49,380 --> 00:10:50,960
And so we need a
nomenclature that

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00:10:50,960 --> 00:10:55,020
allows us to describe
what's going on here.

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00:10:55,020 --> 00:10:57,350
And so the simplest
nomenclature is

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00:10:57,350 --> 00:11:02,480
as follows, where we basically
have the number of carbons

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00:11:02,480 --> 00:11:05,330
and the fatty acids,
say 18, followed

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00:11:05,330 --> 00:11:09,420
by the number of double bonds.

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00:11:09,420 --> 00:11:14,870
So an 18:1 fatty acid,
that's oleic acid--

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00:11:14,870 --> 00:11:18,650
so 18 carbons long,
one double bond--

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00:11:18,650 --> 00:11:23,660
18:0 would be steric acid--

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00:11:23,660 --> 00:11:29,710
18 carbons long, zero double
bonds; 16:0, palmitate--

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00:11:29,710 --> 00:11:30,970
palmitic acid--

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00:11:30,970 --> 00:11:35,010
16 carbons long,
zero double bonds.

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00:11:35,010 --> 00:11:39,110
So if we have one double
bond, oftentimes this

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00:11:39,110 --> 00:11:52,480
is referred to as a MUFA, or
monounsaturated fatty acid.

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00:11:52,480 --> 00:11:55,210
And, of course, if I
have many double bonds--

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00:11:55,210 --> 00:12:03,370
more than one-- that's a PUFA,
or a polyunsaturated fatty

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00:12:03,370 --> 00:12:04,930
acid--

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00:12:04,930 --> 00:12:07,010
probably heard those terms.

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00:12:07,010 --> 00:12:12,010
So what's an example of a
polyunsaturated fatty acid?

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00:12:12,010 --> 00:12:19,240
Well, a common one is an 18:2
polyunsaturated fatty acids--

189
00:12:19,240 --> 00:12:22,330
18 carbons, two double bonds.

190
00:12:22,330 --> 00:12:26,980
The common biological one
is called linoleic acid--

191
00:12:26,980 --> 00:12:58,100
and CH3-- and so 1, 2 double
bonds, 4, 5, 6, 7, 8, 9, 10,

192
00:12:58,100 --> 00:13:06,110
17, 18 carbons total, 18:2
fatty acid, linoleic acid--

193
00:13:06,110 --> 00:13:15,490
formal name is
octadecadiene oleic acid.

194
00:13:18,380 --> 00:13:20,400
If I make it more unsaturated--

195
00:13:20,400 --> 00:13:42,110
so 18:3-- that is linolenic
acid, or octadecatrienoic acid.

196
00:13:42,110 --> 00:13:48,470
And if I painfully draw
out the entire thing--

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00:14:10,510 --> 00:14:16,890
so we've got 1, 2, 3, double
bonds, 1, 2, 3, 4, 5, 6, 7, 8,

198
00:14:16,890 --> 00:14:20,550
9, 10, 17, 18 carbons total--

199
00:14:20,550 --> 00:14:27,690
18:3 polyunsaturated fatty acid
with three double bonds in it.

200
00:14:27,690 --> 00:14:30,420
In all of these cases,
all of those double bonds

201
00:14:30,420 --> 00:14:33,300
are cis double bonds.

202
00:14:33,300 --> 00:14:39,030
And you'll also notice
that the spacing of them

203
00:14:39,030 --> 00:14:44,250
is not entirely random
either, at least as I drew it.

204
00:14:44,250 --> 00:14:46,710
The first of all is
that these are not

205
00:14:46,710 --> 00:14:48,600
conjugated double
bonds, so you see

206
00:14:48,600 --> 00:14:53,730
that there's a carbon in all
cases between the double bond.

207
00:14:53,730 --> 00:14:58,470
And also, you'll notice that
most of the double bonds are

208
00:14:58,470 --> 00:15:02,160
actually started, if you
count from this end--

209
00:15:02,160 --> 00:15:04,650
from the acid end--

210
00:15:04,650 --> 00:15:09,640
this would be carbon 9 and
10-- so 1 plus 7 is 8, 9, 10.

211
00:15:09,640 --> 00:15:12,240
Each of them-- the first
double bond I put in

212
00:15:12,240 --> 00:15:16,230
is between carbons 9 and
10 going in this direction.

213
00:15:16,230 --> 00:15:21,180
And that's a consequence
of the conserved enzymes

214
00:15:21,180 --> 00:15:24,640
that introduced these double
bonds into the molecule.

215
00:15:24,640 --> 00:15:29,530
Now, obviously this
spacing matters.

216
00:15:29,530 --> 00:15:31,560
And so we need a way
in the nomenclature

217
00:15:31,560 --> 00:15:34,680
in order to denote that.

218
00:15:34,680 --> 00:15:38,430
That is where exactly the
double bonds are located.

219
00:15:38,430 --> 00:15:39,910
And there are sort of two ways.

220
00:15:39,910 --> 00:15:41,550
We can count we can
count from one end.

221
00:15:41,550 --> 00:15:43,480
Or, we can count
from the other end.

222
00:15:43,480 --> 00:15:47,280
Now, the most systematic way--

223
00:15:47,280 --> 00:15:52,530
correct way now is to count
from the carboxylic acid end.

224
00:15:52,530 --> 00:15:56,670
So very similar to sugars,
we counted carbon 1 of sugars

225
00:15:56,670 --> 00:16:00,000
to be the one that was closest
to the end of the molecule

226
00:16:00,000 --> 00:16:02,280
where the carbonyl was located.

227
00:16:02,280 --> 00:16:04,260
So same thing in
fatty acid, so this

228
00:16:04,260 --> 00:16:07,360
would be carbon 1 count
in that direction.

229
00:16:07,360 --> 00:16:14,700
And so the nomenclature would
be then to put it in a delta 9,

230
00:16:14,700 --> 00:16:19,170
would be a double bond between
the 9th and 10th carbon

231
00:16:19,170 --> 00:16:22,150
counting from the
carboxylic acid.

232
00:16:22,150 --> 00:16:28,830
And so the 18:2 fatty acid
I drew here, linoleic acid,

233
00:16:28,830 --> 00:16:34,830
would more precisely be
18:2, delta 9, delta 12.

234
00:16:34,830 --> 00:16:39,630
That's because it's carbon
9, 10, 11, 12-- so carbon 9

235
00:16:39,630 --> 00:16:44,010
and 10 and 12 and 13.

236
00:16:44,010 --> 00:16:51,510
Linolenic acid--
18:3, delta 9 12, 15--

237
00:16:51,510 --> 00:16:57,360
so 9, 10, 11, 12,
13, 14, 15 to say

238
00:16:57,360 --> 00:17:01,800
where the double bonds are
in the polyunsaturated fatty

239
00:17:01,800 --> 00:17:02,610
acids.

240
00:17:02,610 --> 00:17:05,220
As you can see, most
polyunsaturated fatty acids

241
00:17:05,220 --> 00:17:09,200
is a consequence that
they're not conjugated.

242
00:17:09,200 --> 00:17:14,119
You'll see that the double bonds
are placed every three carbons.

243
00:17:14,119 --> 00:17:21,109
Now, this three carbon spacing
is maintained even in the--

244
00:17:21,109 --> 00:17:25,520
often in biology, even in the
exceptions, where the first one

245
00:17:25,520 --> 00:17:28,250
is not between carbon 9 and 10.

246
00:17:28,250 --> 00:17:31,160
And so a classic
example of that is

247
00:17:31,160 --> 00:17:36,450
the polyunsaturated fatty
acid arachidonic acid,

248
00:17:36,450 --> 00:17:45,620
which is a 20 carbine fatty
acid with four double bonds

249
00:17:45,620 --> 00:17:48,980
at carbons 5, 8, 11, and 14.

250
00:17:48,980 --> 00:17:53,570
So arachidonic acid, you
may have heard in the past,

251
00:17:53,570 --> 00:17:56,390
is a key signaling fatty acid.

252
00:17:56,390 --> 00:17:59,750
It's mobilized and
used to generate

253
00:17:59,750 --> 00:18:01,490
some inflammatory mediators.

254
00:18:01,490 --> 00:18:04,430
It's the enzyme that
acts on this to generate

255
00:18:04,430 --> 00:18:07,850
the inflammatory mediators--
is the target of very common

256
00:18:07,850 --> 00:18:12,350
drugs, like aspirin or other
nonsteroidal anti-inflammatory

257
00:18:12,350 --> 00:18:13,190
drugs--

258
00:18:13,190 --> 00:18:15,210
ibuprofen, et cetera.

259
00:18:15,210 --> 00:18:18,230
And this molecule,
drawing it like this,

260
00:18:18,230 --> 00:18:24,740
should fully describe to
you what it would look like.

261
00:18:24,740 --> 00:18:27,710
Now, there's also an
older nomenclature

262
00:18:27,710 --> 00:18:30,980
that numbers fatty
acids to name them

263
00:18:30,980 --> 00:18:32,840
and where the double
bonds are located--

264
00:18:32,840 --> 00:18:36,830
not from the carbonyl side,
but from the other end

265
00:18:36,830 --> 00:18:38,060
of the molecule.

266
00:18:38,060 --> 00:18:39,740
And I mentioned
this nomenclature

267
00:18:39,740 --> 00:18:44,270
because it's still used quite
often in popular culture.

268
00:18:44,270 --> 00:18:47,060
And so to do this,
it's basically--

269
00:18:47,060 --> 00:18:51,030
refers to this, I guess,
as the alpha carbon.

270
00:18:51,030 --> 00:18:53,930
So counting in Greek,
going this direction,

271
00:18:53,930 --> 00:18:57,980
the final carbon in
the fatty acid, omega--

272
00:18:57,980 --> 00:19:00,390
the last letter
the Greek alphabet.

273
00:19:00,390 --> 00:19:02,210
And so if you count
from the other end,

274
00:19:02,210 --> 00:19:08,970
we could also give this
different nomenclature.

275
00:19:08,970 --> 00:19:15,860
And so in this case, our
18:3 linolenic acid, 18:3,

276
00:19:15,860 --> 00:19:28,590
delta 9, 12, 15, we could also
say is 18:3, omega 3, 6, 9.

277
00:19:28,590 --> 00:19:30,690
So now we're counting
from this end--

278
00:19:30,690 --> 00:19:35,700
1, 2, 3, first double
the bond, 4, 5, 6,

279
00:19:35,700 --> 00:19:39,030
next double bond, 7,
8, 9, next double bond.

280
00:19:39,030 --> 00:19:44,890
And so thus, 18:1, by
this nomenclature--

281
00:19:44,890 --> 00:19:52,140
18:1, delta 9, would
be the same as 18:1,

282
00:19:52,140 --> 00:19:57,450
omega 9 because it's obviously
meeting in the middle.

283
00:19:57,450 --> 00:20:04,460
But if we did 18:1, delta 12,
that would be 18:1, omega 6.

284
00:20:04,460 --> 00:20:09,680
18:1, delta 15 would
be 18:1, omega 3.

285
00:20:09,680 --> 00:20:11,570
And so I mention
this because you'll

286
00:20:11,570 --> 00:20:14,900
hear about so-called
omega 3 fatty acids.

287
00:20:14,900 --> 00:20:18,680
The major omega 3 fatty acid
that they're talking about

288
00:20:18,680 --> 00:20:20,600
is linolenic acid.

289
00:20:20,600 --> 00:20:23,900
And it's an omega 3 fatty acid
using the nomenclature counting

290
00:20:23,900 --> 00:20:25,130
from the other side.

291
00:20:25,130 --> 00:20:30,200
Or, you could also say
it's 18:3, delta 9, 12, 15.

292
00:20:30,200 --> 00:20:32,930
Now, I want to mention one
of the reasons you hear about

293
00:20:32,930 --> 00:20:36,410
omega 3 fatty acids
is that, in general,

294
00:20:36,410 --> 00:20:42,320
there are fatty acids such as
those that humans cannot make.

295
00:20:42,320 --> 00:20:44,510
And so we have to get
those from the diet.

296
00:20:44,510 --> 00:20:48,890
And so this is the concept
called essential fatty acids.

297
00:20:48,890 --> 00:20:51,350
And so somewhat like
vitamins, there's

298
00:20:51,350 --> 00:20:53,390
things out there
that our physiology

299
00:20:53,390 --> 00:20:57,620
uses that we have to get
from other organisms making.

300
00:20:57,620 --> 00:21:00,000
And therefore, we
have to eat them.

301
00:21:00,000 --> 00:21:03,110
And so if you hear this
term essential fatty acid,

302
00:21:03,110 --> 00:21:05,840
it's basically referring
to specific fatty acids

303
00:21:05,840 --> 00:21:11,390
where we lack the enzymes to
place all the double bonds

304
00:21:11,390 --> 00:21:15,530
to be in the place where
it's useful for some aspect

305
00:21:15,530 --> 00:21:19,230
of our biology.

306
00:21:19,230 --> 00:21:22,260
Now, lots of nomenclature here--

307
00:21:25,120 --> 00:21:29,500
the reason I discuss this is
because this diversity of chain

308
00:21:29,500 --> 00:21:33,700
length and double bonds creates
different properties and nature

309
00:21:33,700 --> 00:21:38,110
uses these diverse chemical
properties of the fatty acids--

310
00:21:38,110 --> 00:21:40,360
that is, different links
and different degrees

311
00:21:40,360 --> 00:21:44,830
of unsaturation or saturation
positions of the double bonds--

312
00:21:44,830 --> 00:21:47,740
to take advantage
of those properties

313
00:21:47,740 --> 00:21:51,350
to do different
things in biology.

314
00:21:51,350 --> 00:21:54,700
And so a lot of this has to do--
a lot of why fatty acids are

315
00:21:54,700 --> 00:21:58,390
useful is that they are
not soluble in water

316
00:21:58,390 --> 00:22:00,310
or poorly soluble in water.

317
00:22:00,310 --> 00:22:02,920
You know this just from
the common experience

318
00:22:02,920 --> 00:22:04,660
of making salad dressing.

319
00:22:04,660 --> 00:22:07,600
And so you mix the oil in the
vinegar in the salad dressing,

320
00:22:07,600 --> 00:22:12,340
and so the oil is largely
made out of fatty acids,

321
00:22:12,340 --> 00:22:13,660
made out of lipids.

322
00:22:13,660 --> 00:22:19,480
And those fatty acids are not
soluble in the vinegar part,

323
00:22:19,480 --> 00:22:22,630
the water part of the molecule.

324
00:22:22,630 --> 00:22:28,300
Now, the fatty acid themselves--

325
00:22:28,300 --> 00:22:31,270
the chain length and the
number of double bonds

326
00:22:31,270 --> 00:22:34,090
will affect other
properties, such as

327
00:22:34,090 --> 00:22:35,810
the melting temperature.

328
00:22:35,810 --> 00:22:43,510
So in general, the melting
temperature of a fatty acid

329
00:22:43,510 --> 00:22:55,290
will decrease with
shorter chain length

330
00:22:55,290 --> 00:23:04,650
and decrease with more
unsaturation-- so more double

331
00:23:04,650 --> 00:23:05,560
bonds.

332
00:23:05,560 --> 00:23:07,050
So the more double
bonds I put in

333
00:23:07,050 --> 00:23:11,790
and the shorter it is, the
lower the melting temperature.

334
00:23:11,790 --> 00:23:16,860
And so you guys know this,
from just cooking experience,

335
00:23:16,860 --> 00:23:17,980
to be the case.

336
00:23:17,980 --> 00:23:27,890
And so animal fatty acids
tend to be more saturated.

337
00:23:31,400 --> 00:23:33,530
And because they're
more saturated,

338
00:23:33,530 --> 00:23:36,830
they have a higher
melting temperature.

339
00:23:36,830 --> 00:23:39,750
And so they're solids
at room temperature.

340
00:23:39,750 --> 00:23:43,280
So think about it--
animal fat, butter, lard--

341
00:23:43,280 --> 00:23:47,280
these things are solid
at room temperature.

342
00:23:47,280 --> 00:23:49,535
So plant fatty acids--

343
00:23:52,170 --> 00:24:01,440
they tend to be more
unsaturated fatty acids.

344
00:24:01,440 --> 00:24:04,080
And they're liquids
at room temperature.

345
00:24:04,080 --> 00:24:07,200
And you know this because
cooking oil made from plants

346
00:24:07,200 --> 00:24:10,630
is typically a liquid
at room temperature.

347
00:24:10,630 --> 00:24:16,260
Now, you might be
aware that olive oil

348
00:24:16,260 --> 00:24:19,770
has a lot of monounsaturated
fatty acids, a lot of MUFAs.

349
00:24:19,770 --> 00:24:22,780
Olive oil, unlike
other plant oils,

350
00:24:22,780 --> 00:24:24,750
which are more
polyunsaturated fatty acids--

351
00:24:24,750 --> 00:24:26,640
if you put those in
the refrigerator,

352
00:24:26,640 --> 00:24:29,670
the olive oil will
tend to form a solid,

353
00:24:29,670 --> 00:24:32,560
whereas your canola
oil will not.

354
00:24:32,560 --> 00:24:34,200
And that's a
consequence of the fact

355
00:24:34,200 --> 00:24:37,260
that the more unsaturated
fatty acids are,

356
00:24:37,260 --> 00:24:40,990
the lower the
melting temperature.

357
00:24:40,990 --> 00:24:43,200
And so the more
likely it is to be

358
00:24:43,200 --> 00:24:46,320
a liquid or a solid in
the fridge or at room

359
00:24:46,320 --> 00:24:49,860
temperature across these
different fatty acids.

360
00:24:49,860 --> 00:24:51,840
To show here on
the slide, here's

361
00:24:51,840 --> 00:24:54,480
just something I stole
from the textbook.

362
00:24:54,480 --> 00:24:57,420
It basically gives
the composition

363
00:24:57,420 --> 00:25:00,270
of some things you might
be aware of-- so olive oil,

364
00:25:00,270 --> 00:25:01,860
butter, and beef fat.

365
00:25:01,860 --> 00:25:04,380
So you can see as we go
down the spectrum here,

366
00:25:04,380 --> 00:25:09,330
you have longer chain
lengths and a reduction

367
00:25:09,330 --> 00:25:10,950
in the number of double bonds.

368
00:25:10,950 --> 00:25:13,920
And, of course, beef fat,
if you've ever handled it,

369
00:25:13,920 --> 00:25:18,060
is a much firmer solid
at room temperature

370
00:25:18,060 --> 00:25:23,740
than butter, which is of course
solid at room temperature,

371
00:25:23,740 --> 00:25:26,190
whereas olive oil is not.

372
00:25:26,190 --> 00:25:30,030
And that follows this
with the chain length

373
00:25:30,030 --> 00:25:32,190
and the double bonds
really affecting

374
00:25:32,190 --> 00:25:36,030
the melting temperature
of these different fats.

375
00:25:36,030 --> 00:25:37,860
Just a couple of sides
so you can better

376
00:25:37,860 --> 00:25:39,780
understand your food--

377
00:25:39,780 --> 00:25:43,020
and so you may have
heard about or seen

378
00:25:43,020 --> 00:25:50,670
on the side of your food
packaging hydrogenated oils.

379
00:25:50,670 --> 00:25:53,940
So what's a hydrogenated oil?

380
00:25:53,940 --> 00:25:55,860
Well, that's basically
taking a plant

381
00:25:55,860 --> 00:26:03,090
oil, which has unsaturated fatty
acids and hydrogenating it.

382
00:26:03,090 --> 00:26:05,038
That is adding hydrogen.

383
00:26:05,038 --> 00:26:05,830
Well, what is that?

384
00:26:05,830 --> 00:26:07,830
It's not really the
hydrogen that's being added.

385
00:26:07,830 --> 00:26:09,660
It's adding electrons
so it's taking it

386
00:26:09,660 --> 00:26:14,310
from being a unsaturated fatty
acid to chemically making

387
00:26:14,310 --> 00:26:16,230
it a saturated fatty acid.

388
00:26:16,230 --> 00:26:17,970
And it's a way to
take plant oils

389
00:26:17,970 --> 00:26:20,880
and make it such that it's
solid at room temperature.

390
00:26:20,880 --> 00:26:24,870
An example of a hydrogenated
oil would be margarine--

391
00:26:24,870 --> 00:26:30,990
plant oil that would be liquid,
reduce it chemically such

392
00:26:30,990 --> 00:26:35,010
that it's fully saturated,
and now it's a solid at room

393
00:26:35,010 --> 00:26:37,000
temperature.

394
00:26:37,000 --> 00:26:42,130
Sure you've also heard
of so-called trans fats.

395
00:26:42,130 --> 00:26:45,520
So what's a trans fat
other than something

396
00:26:45,520 --> 00:26:47,530
cooked up in the
devil's kitchen?

397
00:26:47,530 --> 00:26:51,220
So trans fats are
basically taking animal

398
00:26:51,220 --> 00:26:55,690
fat and introducing chemically
double bonds into them such

399
00:26:55,690 --> 00:26:58,930
that you have this solid
that is now a liquid at room

400
00:26:58,930 --> 00:27:00,230
temperature.

401
00:27:00,230 --> 00:27:04,290
Now, this is done chemically to
introduce those double bonds.

402
00:27:04,290 --> 00:27:07,240
And so if you're introducing
a double bond chemically

403
00:27:07,240 --> 00:27:10,150
by oxidizing the
fatty acid, you'll

404
00:27:10,150 --> 00:27:12,550
get some cis and some trans.

405
00:27:12,550 --> 00:27:15,310
Cis is what biology does
because it introduces them

406
00:27:15,310 --> 00:27:16,390
with an enzyme.

407
00:27:16,390 --> 00:27:18,730
Trans versus cis
is not controlled

408
00:27:18,730 --> 00:27:20,230
when it's done chemically.

409
00:27:20,230 --> 00:27:23,800
And so this leads
to these unnatural

410
00:27:23,800 --> 00:27:28,570
trans fatty acids, which
lead to health issues

411
00:27:28,570 --> 00:27:30,530
and are now banned
in many cities,

412
00:27:30,530 --> 00:27:34,750
including here in
Cambridge, Massachusetts.

413
00:27:34,750 --> 00:27:38,020
Last aside is-- as all of
us have probably experienced

414
00:27:38,020 --> 00:27:41,590
our oils or fats going rancid--

415
00:27:41,590 --> 00:27:42,370
so what is that?

416
00:27:42,370 --> 00:27:47,855
So that's oxygen
oxidizing the fatty acid.

417
00:27:47,855 --> 00:27:50,230
And so if you want to protect
your oil from going rancid,

418
00:27:50,230 --> 00:27:52,540
the thing to do is just
keep it sealed, right?

419
00:27:52,540 --> 00:27:54,820
Keep oxygen away
from it and your oil

420
00:27:54,820 --> 00:27:58,490
will last a lot longer.

421
00:27:58,490 --> 00:28:01,340
So that's fatty acids.

422
00:28:01,340 --> 00:28:04,490
In biology, most fatty
acids aren't sitting around

423
00:28:04,490 --> 00:28:05,690
by themselves.

424
00:28:05,690 --> 00:28:08,090
They're esterified
to an alcohol.

425
00:28:08,090 --> 00:28:11,540
And as we mentioned
in an earlier lecture,

426
00:28:11,540 --> 00:28:17,720
a lipid equals a
fatty acid that's

427
00:28:17,720 --> 00:28:23,915
esterified to an alcohol.

428
00:28:28,010 --> 00:28:31,190
So we spent some time in
the prior lecture talking

429
00:28:31,190 --> 00:28:35,540
about doing this to
make phospholipids.

430
00:28:35,540 --> 00:28:39,890
And that's an example of a
lipid-- fatty acids esterified

431
00:28:39,890 --> 00:28:44,210
to make this phospholipid,
which gave us

432
00:28:44,210 --> 00:28:46,910
both a polar and a
nonpolar end and allowed

433
00:28:46,910 --> 00:28:48,450
us to create membranes.

434
00:28:48,450 --> 00:28:51,830
And so lipids have lots of
important functions in cells.

435
00:28:51,830 --> 00:28:55,850
And so there's the
barrier function, which

436
00:28:55,850 --> 00:28:59,180
is basically membranes,
things like phospholipids

437
00:28:59,180 --> 00:29:01,430
we talked about last time.

438
00:29:01,430 --> 00:29:05,520
There's also signaling
functions of lipids.

439
00:29:05,520 --> 00:29:10,430
So I mentioned
arachidonic acid earlier.

440
00:29:10,430 --> 00:29:12,530
You'll certainly encounter
signaling functions

441
00:29:12,530 --> 00:29:16,370
of lipids in other courses.

442
00:29:16,370 --> 00:29:19,700
And then the last
one, which is really

443
00:29:19,700 --> 00:29:21,890
the reason why we
talk about it now,

444
00:29:21,890 --> 00:29:26,720
is lipids are great
for energy storage

445
00:29:26,720 --> 00:29:31,310
because it's the most
reduced carbons, so the most

446
00:29:31,310 --> 00:29:36,830
dense way to store
energy as reduced carbon.

447
00:29:36,830 --> 00:29:41,830
So the simplest
lipid and the one

448
00:29:41,830 --> 00:29:44,380
used for energy
storage is referred

449
00:29:44,380 --> 00:29:58,352
to as a triacylglyceride,
often abbreviated as a TAG--

450
00:29:58,352 --> 00:29:59,060
triacylglyceride.

451
00:29:59,060 --> 00:30:03,830
And we can see now how we
can make a triacylglyceride

452
00:30:03,830 --> 00:30:07,910
as well as how it relates to
other pathways in metabolism

453
00:30:07,910 --> 00:30:09,330
that we've encountered.

454
00:30:09,330 --> 00:30:13,610
And so here's our old
friend from glycolysis.

455
00:30:18,840 --> 00:30:21,270
Hopefully you
recognize this molecule

456
00:30:21,270 --> 00:30:28,170
as the phosphorylated
triose dihydroxyacetone

457
00:30:28,170 --> 00:30:32,010
phosphate, also an
intermediate in glycolysis.

458
00:30:32,010 --> 00:30:40,695
And so if we reduce this
ketone to the alcohol--

459
00:30:44,090 --> 00:30:50,140
so two electrons from NADH.

460
00:30:50,140 --> 00:30:54,950
Reduce that ketone, that will
oxidize the NADH to NAD+.

461
00:30:54,950 --> 00:30:59,680
If we also remove the
phosphate, now what do we have?

462
00:30:59,680 --> 00:31:02,350
Now we have the alcohol.

463
00:31:05,240 --> 00:31:10,750
And this molecule is glycerol.

464
00:31:10,750 --> 00:31:14,440
And so now this glycerol,
as we talked about before,

465
00:31:14,440 --> 00:31:18,880
we can take three fatty
acids, esterify them

466
00:31:18,880 --> 00:31:20,605
to each of those alcohols.

467
00:31:39,590 --> 00:31:44,270
And now we have a
glycerol molecule

468
00:31:44,270 --> 00:31:49,280
with three fatty acids
esterified to the alcohols

469
00:31:49,280 --> 00:31:50,820
on the glycerol.

470
00:31:50,820 --> 00:31:53,660
This is a triacylglyceride.

471
00:31:53,660 --> 00:31:58,410
Now, of course triacylglycerides
are not soluble in water.

472
00:31:58,410 --> 00:32:03,740
And so when we make these
in cells for energy storage,

473
00:32:03,740 --> 00:32:08,820
they're stored as
so-called lipid droplets.

474
00:32:08,820 --> 00:32:11,960
And so if you look here at
the slide, here's an example.

475
00:32:11,960 --> 00:32:15,650
This up here is an
adipocyte from an animal.

476
00:32:15,650 --> 00:32:19,290
This down here, I
think, is a plant cell.

477
00:32:19,290 --> 00:32:25,970
And so in both cases, you
have these large droplets

478
00:32:25,970 --> 00:32:30,380
that would be basically
droplets of triacylglycerides

479
00:32:30,380 --> 00:32:34,770
that basically form as a way
for long-term energy storage.

480
00:32:34,770 --> 00:32:38,720
And so while we think
of, at least as people,

481
00:32:38,720 --> 00:32:43,700
our adipocytes, our fat cells,
as storing our fat, they do.

482
00:32:43,700 --> 00:32:45,770
But they're really
specialized cell types

483
00:32:45,770 --> 00:32:48,380
that have these
giant lipid droplets,

484
00:32:48,380 --> 00:32:51,440
whereas many cells actually
have much smaller lipid

485
00:32:51,440 --> 00:32:57,110
droplets as a way to
store triacylglycerides

486
00:32:57,110 --> 00:33:01,505
as a way to store energy
as reduced carbon.

487
00:33:04,870 --> 00:33:06,670
I also want to say
that if you look

488
00:33:06,670 --> 00:33:09,460
at this, unlike the
phospholipids that we described

489
00:33:09,460 --> 00:33:12,340
earlier as ways to
build membranes,

490
00:33:12,340 --> 00:33:14,440
these don't have
a charge on them.

491
00:33:14,440 --> 00:33:16,240
And so they're
sometimes referred to

492
00:33:16,240 --> 00:33:20,380
as so-called neutral lipids.

493
00:33:20,380 --> 00:33:22,270
And it's really
this neutral lipids

494
00:33:22,270 --> 00:33:27,370
that allow them to clump
together in these oil

495
00:33:27,370 --> 00:33:30,850
particles, if you will-- these
lipid droplets in cells that

496
00:33:30,850 --> 00:33:34,310
are good for energy storage.

497
00:33:34,310 --> 00:33:36,910
Now, why specifically
are neutral

498
00:33:36,910 --> 00:33:38,470
lipids good for energy storage?

499
00:33:38,470 --> 00:33:41,170
Well, really
chemically dense way

500
00:33:41,170 --> 00:33:43,720
to store energy, the
most reduced carbon.

501
00:33:43,720 --> 00:33:49,150
And by forming these
droplets, not unlike the oil

502
00:33:49,150 --> 00:33:53,050
in your salad dressing, another
neutral lipid forming droplets

503
00:33:53,050 --> 00:33:56,080
within the vinegar,
this is a way

504
00:33:56,080 --> 00:33:58,810
that you store reduced
carbon without having

505
00:33:58,810 --> 00:34:00,950
to carry around water.

506
00:34:00,950 --> 00:34:04,870
And so if we store energy
as carbohydrates, starch

507
00:34:04,870 --> 00:34:08,989
or glycogen, these molecules
have to exist in water.

508
00:34:08,989 --> 00:34:11,500
So you're carrying around
the starch and glycogen.

509
00:34:11,500 --> 00:34:14,620
But as an animal, we're also
carrying around the water.

510
00:34:14,620 --> 00:34:18,699
If we're carrying around
reduced carbon as lipids,

511
00:34:18,699 --> 00:34:21,100
we can now exclude
the water from it.

512
00:34:21,100 --> 00:34:22,600
And so it's much more dense.

513
00:34:22,600 --> 00:34:24,580
And we can, in a
more efficient way,

514
00:34:24,580 --> 00:34:29,350
carry around this
material without having

515
00:34:29,350 --> 00:34:30,230
to carry the water.

516
00:34:30,230 --> 00:34:34,420
And so gram for gram, fat
is a much more efficient way

517
00:34:34,420 --> 00:34:39,429
to pack on calories that we
can burn later than storing

518
00:34:39,429 --> 00:34:41,710
it as carbohydrate.

519
00:34:41,710 --> 00:34:45,310
Fat's also nice because
it forms a nice insulator.

520
00:34:45,310 --> 00:34:46,330
And so it makes sense.

521
00:34:46,330 --> 00:34:48,699
As animals, we need to
survive the winter--

522
00:34:48,699 --> 00:34:50,980
pack on all kinds
of calories as fat,

523
00:34:50,980 --> 00:34:53,469
don't have to carry
around as water.

524
00:34:53,469 --> 00:34:56,170
Just have the energy
there as reduced carbon,

525
00:34:56,170 --> 00:34:57,970
and then we can
slowly release it

526
00:34:57,970 --> 00:35:01,000
over the course of
the winter, as well as

527
00:35:01,000 --> 00:35:05,620
use it to keep us warm, and
then build up those stores again

528
00:35:05,620 --> 00:35:10,060
during the summer months when
there's more food available.

529
00:35:10,060 --> 00:35:14,650
Fat, of course, has months
worth of energy packed into it,

530
00:35:14,650 --> 00:35:18,790
whereas carbohydrates that we
carry around-- our glycogen--

531
00:35:18,790 --> 00:35:20,960
has less than a day's
worth of energy.

532
00:35:20,960 --> 00:35:24,970
So we could live off of
our fat for the winter.

533
00:35:24,970 --> 00:35:28,640
We can't live off of our
glycogen for the winter.

534
00:35:28,640 --> 00:35:30,340
Now, the big trade-off
here is that it's

535
00:35:30,340 --> 00:35:32,290
much slower to mobilize fat.

536
00:35:32,290 --> 00:35:35,200
We have to get into
these lipid droplets

537
00:35:35,200 --> 00:35:37,240
and break off
little pieces of it,

538
00:35:37,240 --> 00:35:40,450
get them into aqueous
water soluble pieces

539
00:35:40,450 --> 00:35:42,550
to break it down.

540
00:35:42,550 --> 00:35:44,650
Glycogen, of course,
is already in water,

541
00:35:44,650 --> 00:35:46,670
can break it down much faster.

542
00:35:46,670 --> 00:35:49,360
And so it's much slower
to mobilize the fat.

543
00:35:49,360 --> 00:35:52,390
But it can be much
more efficient

544
00:35:52,390 --> 00:35:56,230
in terms of what's
stored, whereas glycogen

545
00:35:56,230 --> 00:35:58,240
can be mobilized a lot faster.

546
00:35:58,240 --> 00:36:00,040
And that's really part
of our physiology.

547
00:36:00,040 --> 00:36:02,080
You will burn your
glycogen first

548
00:36:02,080 --> 00:36:07,510
when you exercise before you
start burning a lot of fat.

549
00:36:07,510 --> 00:36:09,880
And I think many
have heard about that

550
00:36:09,880 --> 00:36:14,110
from just reading and thinking
about what you know about

551
00:36:14,110 --> 00:36:18,260
exercise physiology.

552
00:36:18,260 --> 00:36:21,850
Now again, I want
to make the point

553
00:36:21,850 --> 00:36:26,710
that we all know that fat
has more calories than sugar.

554
00:36:26,710 --> 00:36:29,030
And the reason for
that is, to be clear,

555
00:36:29,030 --> 00:36:31,600
is because it's more reduced.

556
00:36:31,600 --> 00:36:34,330
And so the energy that's
released from burning fat,

557
00:36:34,330 --> 00:36:37,540
just like the energy that's
released from burning sugar,

558
00:36:37,540 --> 00:36:41,530
comes because the
transfer of electrons

559
00:36:41,530 --> 00:36:46,100
from the reduced hydrocarbon
to oxygen is favorable.

560
00:36:46,100 --> 00:36:49,160
And that is how
energy is released.

561
00:36:49,160 --> 00:36:52,030
And so fat is more
reduced than sugar,

562
00:36:52,030 --> 00:36:56,590
and so more electrons
to transfer, and so more

563
00:36:56,590 --> 00:37:00,400
energy released
than burning sugar.

564
00:37:00,400 --> 00:37:05,020
So now let's go through, in a
pathway sense, how does nature,

565
00:37:05,020 --> 00:37:07,750
rather than taking gasoline
and just igniting and releasing

566
00:37:07,750 --> 00:37:11,650
a lot of energy, how
does nature stepwise

567
00:37:11,650 --> 00:37:15,580
break down fatty acids in a
way that energy release can

568
00:37:15,580 --> 00:37:18,280
be controlled in the
same way we described it

569
00:37:18,280 --> 00:37:22,960
for carbohydrates-- glycolysis
in the TSA cycle, controlled

570
00:37:22,960 --> 00:37:25,270
stepwise energy release
that can be captured

571
00:37:25,270 --> 00:37:27,240
to do things like make ATP.

572
00:37:30,320 --> 00:37:36,160
How does the same thing work
for oxidation of fatty acids?

573
00:37:36,160 --> 00:37:40,420
Well, if as organisms
we store fatty acids

574
00:37:40,420 --> 00:37:44,620
in these triacylglycerides
or other neutral lipids,

575
00:37:44,620 --> 00:37:50,260
the first step is we have to get
them out of the neutral lipids.

576
00:37:50,260 --> 00:37:55,000
And so if we start with
a triacylglyceride,

577
00:37:55,000 --> 00:37:59,570
the first step is to
use a lipase molecule.

578
00:37:59,570 --> 00:38:03,040
So a lipase just
breaks that ester bond.

579
00:38:03,040 --> 00:38:16,280
And so you basically
now have glycerol

580
00:38:16,280 --> 00:38:20,340
plus the three fatty acids.

581
00:38:20,340 --> 00:38:26,870
We're going to spend
most of our time

582
00:38:26,870 --> 00:38:29,500
today discussing how you
break down the fatty acids.

583
00:38:29,500 --> 00:38:31,880
However, I want to
mention, it should be clear

584
00:38:31,880 --> 00:38:34,760
how you're also going to
metabolize the glycerol.

585
00:38:34,760 --> 00:38:39,755
So glycerol-- we can
oxidize the glycerol.

586
00:38:43,550 --> 00:38:47,750
So now if we oxidize
that alcohol,

587
00:38:47,750 --> 00:38:49,260
what are we going to get?

588
00:38:49,260 --> 00:38:59,470
We're going to get
dihydroxyacetone.

589
00:38:59,470 --> 00:39:07,510
And then if we phosphorylate one
of the ends of that with ATP,

590
00:39:07,510 --> 00:39:11,380
now we get
dihydroxyacetone phosphate.

591
00:39:11,380 --> 00:39:20,590
And that, of course,
can go into glycolysis,

592
00:39:20,590 --> 00:39:23,260
generate pyruvate,
generate acetyl-CoA,

593
00:39:23,260 --> 00:39:26,650
oxidize that acetyl-CoA
in the TCA cycle,

594
00:39:26,650 --> 00:39:30,250
get energy from the
glycerol part of the lipid.

595
00:39:33,080 --> 00:39:35,780
So what about oxidizing
the fatty acids?

596
00:39:35,780 --> 00:39:38,840
Well, the first thing
we have to talk about

597
00:39:38,840 --> 00:39:42,230
to oxidize the fatty
acids is, where is this

598
00:39:42,230 --> 00:39:44,460
going to occur in the cell?

599
00:39:44,460 --> 00:39:48,780
And so lipid droplets are
floating out there in the cell.

600
00:39:48,780 --> 00:39:54,230
And so you mobilize these
pieces with the lipase.

601
00:39:54,230 --> 00:39:57,560
Well, the glycerol now is
sitting there in the cytosol.

602
00:39:57,560 --> 00:40:01,250
That can form the hydroxy
dihydroxyacetone phosphate

603
00:40:01,250 --> 00:40:05,450
and be burned in glycolysis,
which is in the cytosol.

604
00:40:05,450 --> 00:40:07,700
But once we generate
that pyruvate-- remember

605
00:40:07,700 --> 00:40:10,580
that pyruvate had to get
into the mitochondria

606
00:40:10,580 --> 00:40:12,560
where we turned it
into acetyl-CoA.

607
00:40:12,560 --> 00:40:17,240
So acetyl-CoA was present
in the mitochondrial matrix.

608
00:40:17,240 --> 00:40:26,830
So that is here in the
matrix of the mitochondria

609
00:40:26,830 --> 00:40:29,050
where the TCA cycle
happens-- remember,

610
00:40:29,050 --> 00:40:32,660
glycolysis in the cytosol,
TCA cycle in the matrix.

611
00:40:32,660 --> 00:40:35,690
And so that pyruvate eight
needed to get into the matrix.

612
00:40:35,690 --> 00:40:38,050
So we could turn
it into acetyl-CoA.

613
00:40:38,050 --> 00:40:40,630
And then that acetyl-CoA
was in the right place

614
00:40:40,630 --> 00:40:47,770
to be entered into the TCA
cycle and turned into CO2.

615
00:40:47,770 --> 00:40:51,380
Well, fatty acid oxidation
has the same thing.

616
00:40:51,380 --> 00:40:53,830
And so if those fatty acids
are generated out here

617
00:40:53,830 --> 00:40:56,770
in the cytosol when
they're lipases remove them

618
00:40:56,770 --> 00:40:59,110
from the lipid
droplet, it turns out

619
00:40:59,110 --> 00:41:01,600
we're going to burn
the acetyl-CoA we

620
00:41:01,600 --> 00:41:04,120
get from the breakdown
of the fatty acids.

621
00:41:04,120 --> 00:41:06,600
That acetyl-CoA needs
to be in the matrix

622
00:41:06,600 --> 00:41:09,410
so it has access
to the TCA cycle.

623
00:41:09,410 --> 00:41:13,630
And so we need to get the
fatty acid from the cytosol

624
00:41:13,630 --> 00:41:16,360
inside the mitochondria.

625
00:41:16,360 --> 00:41:18,820
Now, part of this--
remember, our CoA

626
00:41:18,820 --> 00:41:22,370
group that I drew last time
is this giant molecule.

627
00:41:22,370 --> 00:41:25,360
And so acetyl-CoA is not
this little two carbon unit.

628
00:41:25,360 --> 00:41:27,410
It's this big, giant molecule.

629
00:41:27,410 --> 00:41:30,850
And so by generating the
acetyl-CoA in the mitochondria,

630
00:41:30,850 --> 00:41:33,310
we obviate the need
to get this giant CoA

631
00:41:33,310 --> 00:41:36,610
group across the
mitochondrial membranes.

632
00:41:36,610 --> 00:41:38,080
But, of course,
we do need to get

633
00:41:38,080 --> 00:41:43,070
the fatty acid into the
right location as well.

634
00:41:43,070 --> 00:41:46,120
And so the way that
that fatty acid

635
00:41:46,120 --> 00:41:49,390
is transported there is
actually via a system

636
00:41:49,390 --> 00:41:52,510
called the carnitine shuttle.

637
00:41:52,510 --> 00:41:56,200
But there's sort of a little bit
of a roundabout way to do it.

638
00:41:56,200 --> 00:41:57,940
And that is, we
are going to need

639
00:41:57,940 --> 00:42:02,020
to do two things-- get the fatty
acid inside the mitochondria

640
00:42:02,020 --> 00:42:09,350
as well as activate it
with this coenzyme A group.

641
00:42:09,350 --> 00:42:15,340
And it turns out that
the fatty acid is first

642
00:42:15,340 --> 00:42:20,470
activated in the cytosol
by adding the coenzyme A

643
00:42:20,470 --> 00:42:25,630
group to the acid on the end,
very much like acetyl-CoA.

644
00:42:25,630 --> 00:42:40,190
And so here is some generic
chain length fatty acid.

645
00:42:40,190 --> 00:42:44,980
And it turns out that
there's an enzyme called

646
00:42:44,980 --> 00:42:57,940
acyl-CoA synthetase
that is going

647
00:42:57,940 --> 00:43:10,460
to take ATP and adenylate this
acid group on the fatty acid.

648
00:43:26,030 --> 00:43:31,820
And so this is
basically an AMP that's

649
00:43:31,820 --> 00:43:37,030
been used to adenylate
the fatty acid itself.

650
00:43:37,030 --> 00:43:38,720
Now, you'll notice
by doing this,

651
00:43:38,720 --> 00:43:41,030
we generate a pyrophosphate.

652
00:43:41,030 --> 00:43:43,700
And that pyrophosphate
can be turned

653
00:43:43,700 --> 00:43:46,040
into two inorganic phosphates--

654
00:43:46,040 --> 00:43:47,690
same trick we've
seen before that

655
00:43:47,690 --> 00:43:51,140
basically can pull a
reaction that otherwise

656
00:43:51,140 --> 00:43:52,580
would be unfavorable forward.

657
00:43:52,580 --> 00:43:58,860
In this case, it's adding the
CoA group to this fatty acid.

658
00:43:58,860 --> 00:44:11,880
And what happens next is that
CoA comes in and replaces

659
00:44:11,880 --> 00:44:30,870
the AMP such that you generate
this fatty acyl-CoA molecule,

660
00:44:30,870 --> 00:44:36,010
which is basically acetyl-CoA
but with some arbitrary longer

661
00:44:36,010 --> 00:44:40,560
a number of reduced hydrocarbons
in the chain-- so not

662
00:44:40,560 --> 00:44:44,010
a 2-carbon unit, but a fatty
acid-- a many carbon unit

663
00:44:44,010 --> 00:44:47,580
fatty acid with whatever
other properties happen

664
00:44:47,580 --> 00:44:50,010
to be on fatty
acid, where now you

665
00:44:50,010 --> 00:44:54,600
have this fatty acyl-CoA
instead of the fatty acid.

666
00:44:54,600 --> 00:44:57,110
So it turns out this
fatty acyl-CoA then

667
00:44:57,110 --> 00:45:02,060
is subjected to a shuttle
called the carnitine shuttle

668
00:45:02,060 --> 00:45:06,200
to actually get it
into the mitochondria.

669
00:45:06,200 --> 00:45:10,040
And so what is carnitine?

670
00:45:10,040 --> 00:45:15,770
So carnitine is a
small molecule--

671
00:45:15,770 --> 00:45:16,505
looks like this.

672
00:45:38,290 --> 00:45:41,280
So this here is carnitine.

673
00:45:41,280 --> 00:45:48,890
And it turns out that this
hydroxyl group, basically,

674
00:45:48,890 --> 00:45:55,550
is swapped for the CoA
on the fatty acyl-CoA.

675
00:45:55,550 --> 00:46:37,580
And so if this here is
some generic fatty CoA,

676
00:46:37,580 --> 00:46:40,730
you end up with this
molecule, which is

677
00:46:40,730 --> 00:46:50,320
called a fatty acyl carnitine.

678
00:46:50,320 --> 00:46:55,390
So all I've done is take the
CoA off and move the fatty acid

679
00:46:55,390 --> 00:47:00,850
to make this ester here with
the alcohol on the carnitine.

680
00:47:00,850 --> 00:47:05,800
And this fatty acyl
carnitine can now

681
00:47:05,800 --> 00:47:11,740
be transported across the
mitochondrial membrane-- so

682
00:47:11,740 --> 00:47:14,470
from the cytosol to
the mitochondria.

683
00:47:14,470 --> 00:47:19,390
Here we have our
fatty acyl carnitine.

684
00:47:19,390 --> 00:47:23,560
And then that fatty
acyl carnitine

685
00:47:23,560 --> 00:47:30,890
can exchange a CoA
for the carnitine

686
00:47:30,890 --> 00:47:36,120
and regenerate
the fatty acyl-CoA

687
00:47:36,120 --> 00:47:38,550
in the mitochondrial matrix.

688
00:47:38,550 --> 00:47:43,890
This whole process is referred
to as the carnitine shuttle

689
00:47:43,890 --> 00:47:50,910
and is effectively a complex
way to move fatty acyl-CoAs

690
00:47:50,910 --> 00:47:53,430
from the cytosol into
the mitochondria, where

691
00:47:53,430 --> 00:47:54,990
they can be oxidized.

692
00:47:54,990 --> 00:47:57,930
Here's another picture
of it that is maybe

693
00:47:57,930 --> 00:48:00,210
drawn in a different
way because it's

694
00:48:00,210 --> 00:48:02,700
a little bit confusing
as something to describe,

695
00:48:02,700 --> 00:48:11,190
but basically you generate this
fatty acyl-CoA in the cytosol.

696
00:48:11,190 --> 00:48:15,150
And then the fatty
acyl-CoA is exchanged

697
00:48:15,150 --> 00:48:16,800
for a fatty acyl carnitine.

698
00:48:16,800 --> 00:48:19,080
Fatty acyl carnitine
goes into the matrix

699
00:48:19,080 --> 00:48:22,920
and is used to regenerate
the fatty acyl-CoA.

700
00:48:22,920 --> 00:48:24,630
The enzymes that do
this is something

701
00:48:24,630 --> 00:48:27,900
called CPT, or carnitine
palmitoyltransferase.

702
00:48:32,940 --> 00:48:47,630
Write that down-- carnitine,
which is obviously refers

703
00:48:47,630 --> 00:48:51,260
to palmitate as the
common fatty acid,

704
00:48:51,260 --> 00:48:55,250
although CPT will catalyze
many fatty acyl carnitine,

705
00:48:55,250 --> 00:48:57,620
fatty acyl-CoA interconversions.

706
00:48:57,620 --> 00:48:59,390
And so by doing
that interconversion

707
00:48:59,390 --> 00:49:02,210
on the cytosolic side and
the mitochondrial side,

708
00:49:02,210 --> 00:49:05,030
you can use
carnitine as a handle

709
00:49:05,030 --> 00:49:10,145
to transfer fatty acyl-CoAs
from one compartment to another.

710
00:49:13,800 --> 00:49:17,760
Now, once that fatty acyl-CoA
is in the mitochondria,

711
00:49:17,760 --> 00:49:23,670
it can now be oxidized
to acetyl-CoA.

712
00:49:27,440 --> 00:49:30,860
So now, let's discuss
the series of steps

713
00:49:30,860 --> 00:49:34,430
that is referred to as
fatty acid oxidation,

714
00:49:34,430 --> 00:49:36,680
and abbreviated FAO.

715
00:49:36,680 --> 00:49:48,080
And so, of course, we start here
with our generic fatty acyl-CoA

716
00:49:48,080 --> 00:49:54,920
in the matrix of the
mitochondria of some arbitrary

717
00:49:54,920 --> 00:49:57,470
chain length.

718
00:49:57,470 --> 00:50:00,890
And so the first thing
that we're going to do

719
00:50:00,890 --> 00:50:04,730
is oxidize this
carbon-carbon bond--

720
00:50:04,730 --> 00:50:08,810
that is, introduce
a double bond here.

721
00:50:08,810 --> 00:50:10,460
That's an oxidation reaction.

722
00:50:10,460 --> 00:50:12,920
It's exactly the
same reaction that we

723
00:50:12,920 --> 00:50:18,560
saw convert succinate to
fumerate in the TCA cycle.

724
00:50:18,560 --> 00:50:26,100
That reaction used FAD
as an electron acceptor.

725
00:50:26,100 --> 00:50:29,570
So we oxidize that
carbon-carbon bond, FAD

726
00:50:29,570 --> 00:50:32,310
gets reduced to FADH2.

727
00:50:38,150 --> 00:51:06,970
This is carried out by an enzyme
called acyl-CoA dehydrogenase

728
00:51:06,970 --> 00:51:10,270
and generates that intermediate.

729
00:51:10,270 --> 00:51:13,030
Again, now just like
we did in the TCA cycle

730
00:51:13,030 --> 00:51:15,730
when we converted
fumerate into malate,

731
00:51:15,730 --> 00:51:20,500
we added water across
this double bond.

732
00:51:20,500 --> 00:51:22,930
Do exactly the same thing here.

733
00:51:39,570 --> 00:51:42,030
That generates
this intermediate.

734
00:51:42,030 --> 00:51:48,210
Now we can oxidize this
carbon here, this alcohol--

735
00:51:48,210 --> 00:51:51,210
oxidize it to the ketone.

736
00:51:51,210 --> 00:51:54,240
Of course, you know
how to do this.

737
00:51:54,240 --> 00:51:57,630
We've now seen it
a million times.

738
00:51:57,630 --> 00:52:02,500
So that generates
this hydride ion,

739
00:52:02,500 --> 00:52:19,496
which can be transferred to
NAD+, reducing it to NADH.

740
00:52:34,170 --> 00:52:46,100
And now what happens next
is CoA basically breaks

741
00:52:46,100 --> 00:52:48,050
that carbon-carbon bond.

742
00:52:48,050 --> 00:52:49,260
And what are we left with?

743
00:52:49,260 --> 00:52:57,710
We're left with over here
release of a acetyl-CoA group,

744
00:52:57,710 --> 00:53:02,810
which can then go down and be
further oxidized in the TCA

745
00:53:02,810 --> 00:53:14,920
cycle as well as this
fatty acyl-CoA that

746
00:53:14,920 --> 00:53:22,090
is two carbons shorter than
the one we started with.

747
00:53:22,090 --> 00:53:27,370
That can then go back up,
repeat the cycle again

748
00:53:27,370 --> 00:53:31,150
until, if you start with
an even number of carbons,

749
00:53:31,150 --> 00:53:36,280
the last one leaves you with
two acetyl-CoA molecules.

750
00:53:36,280 --> 00:53:39,610
And so per two
carbon units that we

751
00:53:39,610 --> 00:53:44,740
run through this cycle of
fatty acid oxidation, what

752
00:53:44,740 --> 00:53:50,250
we get is we get an
acetyl-CoA that comes out,

753
00:53:50,250 --> 00:53:57,420
we get an FADH2,
and we get an NADH.

754
00:53:57,420 --> 00:54:00,720
Now, of course, if we start
with an unsaturated fatty acid,

755
00:54:00,720 --> 00:54:03,150
we don't have to introduce
a double bond into it,

756
00:54:03,150 --> 00:54:07,560
we don't get the FADH2,
we get less energy

757
00:54:07,560 --> 00:54:11,570
produced from that molecule.

758
00:54:11,570 --> 00:54:16,990
And so if this acetyl-CoA goes
on and enters the TCA cycle

759
00:54:16,990 --> 00:54:21,460
and we fully oxidize it to
CO2, we get three more NADH,

760
00:54:21,460 --> 00:54:26,900
we get another FADH2,
and we get a GTP.

761
00:54:26,900 --> 00:54:28,950
It's written up
there as a reminder.

762
00:54:28,950 --> 00:54:34,340
And so with a fully saturated
per two carbons out,

763
00:54:34,340 --> 00:54:40,460
we basically get four NADHs,
two FADH2s, and a GTP.

764
00:54:40,460 --> 00:54:44,330
And that's a fair amount
of energy, if you will,

765
00:54:44,330 --> 00:54:47,600
released from the oxidation
of this fatty acid

766
00:54:47,600 --> 00:54:50,962
all the way to CO2.

767
00:54:50,962 --> 00:54:52,920
We'll come back to that
accounting in a second.

768
00:54:52,920 --> 00:54:54,510
But first I want to
say, what happens

769
00:54:54,510 --> 00:54:57,940
if you happen to start with
an odd number of carbons.

770
00:54:57,940 --> 00:55:00,180
So I mentioned that most
biological fatty acids

771
00:55:00,180 --> 00:55:01,860
have even numbers of carbons.

772
00:55:01,860 --> 00:55:08,280
But there are odd chain
carbon lengths of fatty acids.

773
00:55:08,280 --> 00:55:09,480
Some bacteria make these.

774
00:55:09,480 --> 00:55:11,130
Sometimes it just happens.

775
00:55:11,130 --> 00:55:13,140
Obviously, if you
do that, you'll

776
00:55:13,140 --> 00:55:17,790
end up at the end with
this molecule, which

777
00:55:17,790 --> 00:55:22,900
is a 3-carbon acetyl-CoA
called propionyl-CoA.

778
00:55:27,260 --> 00:55:30,410
And so cells need
a way to deal with

779
00:55:30,410 --> 00:55:33,800
this 3-carbon propionyl-CoA.

780
00:55:33,800 --> 00:55:37,550
Well, the way they deal with
it is they carboxylic it.

781
00:55:37,550 --> 00:55:40,340
So if we're going to
add a CO2 to a molecule,

782
00:55:40,340 --> 00:55:41,460
how do we do that?

783
00:55:41,460 --> 00:55:42,680
Well, we need a co-factor.

784
00:55:42,680 --> 00:55:47,720
Remember, we did this with the
pyruvate carboxylase reaction.

785
00:55:47,720 --> 00:55:49,940
This was the reaction of biotin.

786
00:55:49,940 --> 00:55:52,970
So we started with bicarbonate.

787
00:55:52,970 --> 00:55:56,300
We phosphorylated
the bicarbonate.

788
00:56:03,430 --> 00:56:07,390
And then that
phosphorylated bicarbonate,

789
00:56:07,390 --> 00:56:11,620
there was biotin in the
active site of the enzyme.

790
00:56:11,620 --> 00:56:13,550
That released the phosphate.

791
00:56:13,550 --> 00:56:20,160
I had enzyme biotin
with a CO2 on it.

792
00:56:20,160 --> 00:56:24,710
And so if we take this
propionyl-CoA here,

793
00:56:24,710 --> 00:56:32,590
which is drawn in the keto
form, and we redraw it

794
00:56:32,590 --> 00:56:51,250
in enol form of
the propionyl-CoA,

795
00:56:51,250 --> 00:56:55,000
we carry out similar
reaction that we saw before.

796
00:56:55,000 --> 00:56:57,640
And now we end up
with this molecule.

797
00:57:10,710 --> 00:57:14,720
So, effectively, adding
the CO2 to this carbon

798
00:57:14,720 --> 00:57:16,400
to the second carbon in.

799
00:57:16,400 --> 00:57:21,858
And that's this molecule, which
is called methyl-malonyl-CoA.

800
00:57:27,750 --> 00:57:32,040
I'm going to redraw
methyl-malonyl-CoA just

801
00:57:32,040 --> 00:57:35,490
to show you how
cells deal with this.

802
00:58:08,610 --> 00:58:11,310
So this is methyl-malonyl-CoA.

803
00:58:11,310 --> 00:58:13,260
I just re-drew it in
a way that there's

804
00:58:13,260 --> 00:58:16,020
some colors on the
different molecules.

805
00:58:16,020 --> 00:58:17,850
What I'm going to
do is I'm basically

806
00:58:17,850 --> 00:58:21,810
going to take this
group and this group

807
00:58:21,810 --> 00:58:26,280
and swap their positions.

808
00:58:26,280 --> 00:58:52,710
And if I do that, I will
end up with this molecule,

809
00:58:52,710 --> 00:58:59,270
which hopefully you recognize
as succinyl-CoA from the TCA

810
00:58:59,270 --> 00:59:00,350
cycle.

811
00:59:00,350 --> 00:59:03,680
Now, the mechanism for
how that swap happens,

812
00:59:03,680 --> 00:59:05,790
I don't have time to go into.

813
00:59:05,790 --> 00:59:10,190
But this complex
intermolecular rearrangement

814
00:59:10,190 --> 00:59:11,930
requires a cofactor.

815
00:59:11,930 --> 00:59:15,800
That cofactor comes
from vitamin B12.

816
00:59:15,800 --> 00:59:18,123
And so here's a
picture of vitamin B12.

817
00:59:18,123 --> 00:59:19,790
You can see by looking
at it why I don't

818
00:59:19,790 --> 00:59:21,980
want to draw that out for you.

819
00:59:21,980 --> 00:59:24,890
It's a cobalt-containing
cofactor-- sometimes referred

820
00:59:24,890 --> 00:59:27,080
to as cobalamin.

821
00:59:27,080 --> 00:59:28,790
If you're interested,
you can look up

822
00:59:28,790 --> 00:59:34,490
the chemistry for how
vitamin B12 helps catalyze

823
00:59:34,490 --> 00:59:36,800
this intermolecular
rearrangement

824
00:59:36,800 --> 00:59:40,060
to go from methyl-malonyl-CoA
to succinyl-CoA.

825
00:59:40,060 --> 00:59:42,560
But the important take home is
that if you have an odd chain

826
00:59:42,560 --> 00:59:45,380
fatty acid, use a
biotin-containing enzyme

827
00:59:45,380 --> 00:59:50,150
to carboxylate propionyl-CoA
to methyl-malonyl-CoA, and then

828
00:59:50,150 --> 00:59:53,090
B12 to rearrange that
methyl-malonyl-CoA

829
00:59:53,090 --> 00:59:54,500
to succinyl-CoA.

830
00:59:54,500 --> 01:00:00,860
And now this can enter the TCA
cycle and be oxidized as well.

831
01:00:00,860 --> 01:00:03,380
So now you have
the details of how

832
01:00:03,380 --> 01:00:12,720
you can start with a fatty
acid and oxidize it to CO2.

833
01:00:12,720 --> 01:00:15,750
Now, I think it's
useful if we compare

834
01:00:15,750 --> 01:00:19,950
the output of what we can get
from glucose oxidation to CO2--

835
01:00:19,950 --> 01:00:22,320
carbohydrate oxidation to CO2--

836
01:00:22,320 --> 01:00:25,650
to what we can get if we
start with a fatty acid

837
01:00:25,650 --> 01:00:28,710
and oxidize it to
CO2 and sort of

838
01:00:28,710 --> 01:00:31,770
illustrate that there
are more calories in fat

839
01:00:31,770 --> 01:00:34,110
than there are in sugar.

840
01:00:34,110 --> 01:00:37,590
And so for this
comparison, we'll

841
01:00:37,590 --> 01:00:44,370
compare glucose, which, of
course, has six carbons in it

842
01:00:44,370 --> 01:00:49,410
to a 6:0 fatty acid--

843
01:00:49,410 --> 01:00:51,030
also six carbons.

844
01:00:51,030 --> 01:00:53,970
And what do we get if we
take this less reduced

845
01:00:53,970 --> 01:00:59,655
versus more reduced molecule
and fully oxidize it to CO2?

846
01:01:03,470 --> 01:01:07,730
Well, if we start with glucose--

847
01:01:07,730 --> 01:01:11,500
so if we take that glucose
and we run glycolysis--

848
01:01:11,500 --> 01:01:13,450
and so take that
glucose and turn it

849
01:01:13,450 --> 01:01:17,650
into two pyruvate
molecules, of course

850
01:01:17,650 --> 01:01:25,110
we get from that two
ATPs and two NADHs.

851
01:01:25,110 --> 01:01:30,670
And then if we take those two
pyruvate molecules and turn

852
01:01:30,670 --> 01:01:37,450
them into two acetyl-CoAs
plus two CO2s--

853
01:01:37,450 --> 01:01:40,330
that's the pyruvate
dehydrogenase reaction--

854
01:01:40,330 --> 01:01:43,870
we get two more NADHs.

855
01:01:43,870 --> 01:01:47,890
And then if we take
those two acetyl-CoAs

856
01:01:47,890 --> 01:01:52,150
and turn them into
four CO2s, that's

857
01:01:52,150 --> 01:01:54,490
the TSA cycle,
what do we get out?

858
01:01:54,490 --> 01:01:58,700
We get two GTP molecules.

859
01:01:58,700 --> 01:02:08,540
We get two FADH2 molecules from
the succinate dehydrogenase

860
01:02:08,540 --> 01:02:09,260
step.

861
01:02:09,260 --> 01:02:15,230
And we get 2 times 3
equals 6 more NADHs.

862
01:02:15,230 --> 01:02:22,550
And so our total yield is 4
ATP equivalents-- remember,

863
01:02:22,550 --> 01:02:25,490
the GTPs can be
interconverted with ATP--

864
01:02:25,490 --> 01:02:40,000
two FADH2s, and 6,
7, 8, 9, 10 NADHs.

865
01:02:40,000 --> 01:02:44,650
What if we start with
our 6:0 zero fatty acid?

866
01:02:44,650 --> 01:02:50,710
Well, to metabolize it, first
we have to take that fatty acid

867
01:02:50,710 --> 01:02:54,430
and we have to make
our fatty acyl-CoA.

868
01:02:54,430 --> 01:02:59,960
That's going to cost us two ATP.

869
01:02:59,960 --> 01:03:01,370
Why two ATP?

870
01:03:01,370 --> 01:03:04,940
Because remember when we
charge that fatty acetyl-CoA,

871
01:03:04,940 --> 01:03:09,530
which is now erased,
I think-- yes, it is--

872
01:03:09,530 --> 01:03:11,570
we converted an ATP to an AMP.

873
01:03:11,570 --> 01:03:14,330
And so that's two
ATP equivalents

874
01:03:14,330 --> 01:03:19,850
to charge that fatty
acid to a fatty acyl-CoA.

875
01:03:19,850 --> 01:03:23,070
Next, we take that
fatty acyl-CoA

876
01:03:23,070 --> 01:03:29,080
and we turn it into three
acetyl-CoA molecules

877
01:03:29,080 --> 01:03:32,620
via fatty acid oxidation cycle.

878
01:03:32,620 --> 01:03:39,250
That's two trips around to
generate the three acetyl-CoAs.

879
01:03:39,250 --> 01:03:44,440
So that will give us two
FADH2s and two NADHs.

880
01:03:47,610 --> 01:03:51,450
And then once we have
those three acetyl-CoA,

881
01:03:51,450 --> 01:03:56,390
we can turn them into six
CO2s in the TCA cycle.

882
01:03:56,390 --> 01:04:02,700
So that's three
GTPs, three FADH2s.

883
01:04:02,700 --> 01:04:12,120
And 3 times 3 is 9 NADHs for
a total yield of 3 minus 2

884
01:04:12,120 --> 01:04:30,010
is 1 ATP equivalent,
5 FADHs, and 11 NADHs.

885
01:04:34,220 --> 01:04:38,430
Now, I went through
this exercise

886
01:04:38,430 --> 01:04:42,930
because it's not
immediately apparent

887
01:04:42,930 --> 01:04:46,020
that the yield of
fatty acid oxidation

888
01:04:46,020 --> 01:04:49,320
gives you more energy
from full oxidation

889
01:04:49,320 --> 01:04:53,670
than oxidizing the equivalent
carbohydrate, at least

890
01:04:53,670 --> 01:04:56,040
in terms of ATP.

891
01:04:56,040 --> 01:05:00,450
You get four ATPs directly
from full oxidation of glucose,

892
01:05:00,450 --> 01:05:04,410
whereas you only get one
ATP equivalent directly

893
01:05:04,410 --> 01:05:11,870
from the complete oxidation of
this 6-carbon fatty acyl-CoA.

894
01:05:11,870 --> 01:05:15,530
Now, I say this because most
of the energy, if you will,

895
01:05:15,530 --> 01:05:19,100
that's released from
oxidation of fat and sugar

896
01:05:19,100 --> 01:05:22,010
isn't actually
directly producing ATP.

897
01:05:22,010 --> 01:05:31,640
It's actually being used to
charge up this NADH, and NAD+,

898
01:05:31,640 --> 01:05:43,190
or FADH2/FAD ratios in the cell,
which we will see is also a lot

899
01:05:43,190 --> 01:05:45,830
of energy, because those
electrons can be transferred

900
01:05:45,830 --> 01:05:50,390
to oxygen and be used to do
other work down the road.

901
01:05:50,390 --> 01:05:55,670
Now, your book will tell
you that each of these NADHs

902
01:05:55,670 --> 01:06:00,560
or FADH2s are worth on the
order of one to three ATP.

903
01:06:00,560 --> 01:06:03,320
And I guess this kind
of fits intuitively what

904
01:06:03,320 --> 01:06:06,050
you might guess based on the
thermodynamics of the GAPDH

905
01:06:06,050 --> 01:06:06,630
reaction.

906
01:06:06,630 --> 01:06:08,450
So if you go back
to that, remember

907
01:06:08,450 --> 01:06:14,390
our oxidative phosphorylation
we described at GAPDH

908
01:06:14,390 --> 01:06:18,770
roughly generated an ATP.

909
01:06:18,770 --> 01:06:26,420
And so even if we say one ATP
equals an FADH2 or an NADH,

910
01:06:26,420 --> 01:06:30,380
which, of course, there's not
a direct relationship to that,

911
01:06:30,380 --> 01:06:32,360
you can still,
even with that, say

912
01:06:32,360 --> 01:06:35,930
that our fatty acid oxidation--
if we add up all these numbers,

913
01:06:35,930 --> 01:06:41,760
we would get 17, whereas if
we add up all these numbers,

914
01:06:41,760 --> 01:06:44,190
we get 16.

915
01:06:44,190 --> 01:06:47,900
So I guess that says
that there's more

916
01:06:47,900 --> 01:06:52,520
coming from fatty acid oxidation
than from complete glucose

917
01:06:52,520 --> 01:06:53,840
oxidation.

918
01:06:53,840 --> 01:06:56,630
But you probably also learned
in high school or somewhere else

919
01:06:56,630 --> 01:07:01,220
that NADH gives you
more ATP than FADH2.

920
01:07:01,220 --> 01:07:02,180
That's true.

921
01:07:02,180 --> 01:07:05,640
Our goal is to understand
why that's the case.

922
01:07:05,640 --> 01:07:10,190
And so those numbers
will only get better

923
01:07:10,190 --> 01:07:15,110
for fatty acid oxidation
in terms of ATP equivalents

924
01:07:15,110 --> 01:07:20,550
when we can describe how
to do those conversions.

925
01:07:20,550 --> 01:07:25,970
However, to really appreciate
how these electron carriers

926
01:07:25,970 --> 01:07:30,140
equal energy and equal
biological energy,

927
01:07:30,140 --> 01:07:32,900
we really need to
go back and revisit

928
01:07:32,900 --> 01:07:38,270
some concepts in bioenergetics
and thermodynamics

929
01:07:38,270 --> 01:07:42,350
to really understand what
biological energy is.

930
01:07:42,350 --> 01:07:45,530
And that will also
help us understand

931
01:07:45,530 --> 01:07:48,860
mitochondrial oxidative
phosphorylation, which

932
01:07:48,860 --> 01:07:52,520
is really the process that
allows us to interconvert

933
01:07:52,520 --> 01:07:57,470
these electron carriers
and their ability

934
01:07:57,470 --> 01:08:05,090
to transfer electrons to
oxygen as a way to generate

935
01:08:05,090 --> 01:08:06,990
favorably synthesized ATP.

936
01:08:17,950 --> 01:08:24,020
So hopefully, you will remember
from our previous lectures

937
01:08:24,020 --> 01:08:29,270
that for any reaction, any
pathway, any process to occur,

938
01:08:29,270 --> 01:08:31,729
it has to be thermodynamically
favorable-- that is,

939
01:08:31,729 --> 01:08:34,069
delta G has to be less than 0.

940
01:08:34,069 --> 01:08:37,790
And remember, ATP
to ADP was useful

941
01:08:37,790 --> 01:08:40,350
because that reaction
is very favorable.

942
01:08:40,350 --> 01:08:43,609
And so we could couple ATP to
ADP conversion to otherwise

943
01:08:43,609 --> 01:08:45,930
unfavorable reactions.

944
01:08:45,930 --> 01:08:50,370
And that is what allowed
us to have ATP be useful.

945
01:08:50,370 --> 01:08:55,319
And it was useful because delta
G equals delta G naught prime

946
01:08:55,319 --> 01:09:00,510
plus RT times a
log of the products

947
01:09:00,510 --> 01:09:05,529
of the reaction over the
reactants of the reaction.

948
01:09:05,529 --> 01:09:11,580
And so if ADP is a product
in ATP is a reactant,

949
01:09:11,580 --> 01:09:14,250
it was actually
that ATP/ADP ratio

950
01:09:14,250 --> 01:09:16,840
that was providing the
energy, if you will,

951
01:09:16,840 --> 01:09:19,530
to drive the reaction.

952
01:09:22,500 --> 01:09:27,689
This was also, if you
recall, why we described

953
01:09:27,689 --> 01:09:32,880
that oxidation of reduced
carbon because it was favorable,

954
01:09:32,880 --> 01:09:35,340
was able to be coupled
to reactions that

955
01:09:35,340 --> 01:09:39,870
keep this ATP/ADP ratio high, so
that that high ratio could then

956
01:09:39,870 --> 01:09:44,100
support otherwise
unfavorable reactions.

957
01:09:44,100 --> 01:09:46,170
But now, you
hopefully appreciate

958
01:09:46,170 --> 01:09:52,830
that in reality, most of the
energy from carbon oxidation

959
01:09:52,830 --> 01:09:55,320
is not directly captured as ATP.

960
01:09:55,320 --> 01:09:59,400
It's being used to charge
up these other ratios--

961
01:09:59,400 --> 01:10:03,180
NAD/NADH, FADH2/FAD.

962
01:10:03,180 --> 01:10:07,200
And the energetics of doing that
follow exactly the same rules

963
01:10:07,200 --> 01:10:11,310
as ATP or really
any other reaction.

964
01:10:11,310 --> 01:10:13,680
And effectively,
it's the transfer

965
01:10:13,680 --> 01:10:17,520
of electrons that is
favorable or not that

966
01:10:17,520 --> 01:10:24,360
really is going on
here, just like we

967
01:10:24,360 --> 01:10:28,650
discussed for ATP to ADP.

968
01:10:28,650 --> 01:10:32,340
And so we can couple other
reactions to those ratios

969
01:10:32,340 --> 01:10:37,380
as a way to make other
reactions possible.

970
01:10:37,380 --> 01:10:40,290
Now, ultimately it turns
out that these things,

971
01:10:40,290 --> 01:10:44,640
these redox ratios, are more
useful than ATP because these

972
01:10:44,640 --> 01:10:48,030
electron transfers-- favorable
electron transfers-- remember,

973
01:10:48,030 --> 01:10:51,780
biological energy is all about
oxidation and reduction--

974
01:10:51,780 --> 01:10:53,370
can be used to drive ATP.

975
01:10:53,370 --> 01:10:57,300
We'll see that when we described
how OXPHOS in the mitochondria

976
01:10:57,300 --> 01:10:58,860
really works.

977
01:10:58,860 --> 01:11:01,080
But it can be used for
other things as well.

978
01:11:01,080 --> 01:11:03,030
We'll see we can
use it to make heat.

979
01:11:03,030 --> 01:11:06,270
We can do it other work,
like move ions, et cetera.

980
01:11:06,270 --> 01:11:09,750
And so-- we can even
make glucose, right?

981
01:11:09,750 --> 01:11:10,770
gluconeogenesis.

982
01:11:10,770 --> 01:11:13,200
We needed a source of NADH.

983
01:11:13,200 --> 01:11:16,628
And so ultimately, all
biological energy, of course,

984
01:11:16,628 --> 01:11:17,670
has to come from the sun.

985
01:11:17,670 --> 01:11:22,020
And photosynthesis also is
about capturing solar energy

986
01:11:22,020 --> 01:11:26,190
as these oxidation
and reduction pairs.

987
01:11:26,190 --> 01:11:32,560
And so if we appreciate
this, what we realize

988
01:11:32,560 --> 01:11:34,855
is that it's really these
transfers of electrons.

989
01:11:34,855 --> 01:11:37,730
Remember, there's no free
electrons in biology.

990
01:11:37,730 --> 01:11:41,230
And so it's really coupling
oxidation and reduction

991
01:11:41,230 --> 01:11:43,540
reactions that
are favorable that

992
01:11:43,540 --> 01:11:48,840
ends up being how
bioenergetics largely works.

993
01:11:48,840 --> 01:11:51,010
Now, I like to be
explicit about this

994
01:11:51,010 --> 01:11:53,950
because sometimes
people get confused

995
01:11:53,950 --> 01:11:57,940
by oxidation and reduction
reactions and focus on charge.

996
01:11:57,940 --> 01:12:00,850
And I just want to point
out oxidation and reduction

997
01:12:00,850 --> 01:12:05,260
reactions are really
moving electrons.

998
01:12:05,260 --> 01:12:12,410
And this is
irrelevant of charge.

999
01:12:12,410 --> 01:12:14,990
So I add an electron to
an uncharged molecule,

1000
01:12:14,990 --> 01:12:16,820
I get a negatively
charged molecule.

1001
01:12:16,820 --> 01:12:18,710
Add it to a positively
charged molecule,

1002
01:12:18,710 --> 01:12:20,150
get a neutral molecule.

1003
01:12:20,150 --> 01:12:22,035
Add it to a more positively
charged molecule,

1004
01:12:22,035 --> 01:12:23,660
now have a positively
charged molecule.

1005
01:12:23,660 --> 01:12:25,220
It's adding these electrons.

1006
01:12:25,220 --> 01:12:28,700
Each of these are
reduction reactions.

1007
01:12:28,700 --> 01:12:32,700
In that direction, they
would be oxidation reactions.

1008
01:12:32,700 --> 01:12:41,381
And so NAD+ plus 2
electrons going to NADH,

1009
01:12:41,381 --> 01:12:48,620
FAD plus 2 electrons
going to FADH2--

1010
01:12:48,620 --> 01:12:50,870
all reductions in
this direction, all

1011
01:12:50,870 --> 01:12:55,020
oxidations in that direction.

1012
01:12:55,020 --> 01:12:57,050
Now, because there's
not free electrons,

1013
01:12:57,050 --> 01:12:59,960
these reactions have
to happen in pairs.

1014
01:12:59,960 --> 01:13:02,270
And so if we consider
a pair, here's

1015
01:13:02,270 --> 01:13:06,864
lactate interconversion
with pyruvate.

1016
01:13:09,590 --> 01:13:15,110
So alcohol and lactate to
the ketone and pyruvate--

1017
01:13:15,110 --> 01:13:17,060
this direction is an oxidation.

1018
01:13:19,580 --> 01:13:23,690
That means the electrons
have to go somewhere--

1019
01:13:23,690 --> 01:13:27,320
NAD+ to NADH.

1020
01:13:27,320 --> 01:13:28,340
This is a reduction.

1021
01:13:28,340 --> 01:13:32,240
If we go from pyruvate to
lactate, that's a reduction.

1022
01:13:32,240 --> 01:13:37,370
We can reoxidize
NADH back to NAD+.

1023
01:13:37,370 --> 01:13:40,350
Of course, you'll remember
from glycolysis fermentation,

1024
01:13:40,350 --> 01:13:45,290
this inner conversion
is catalyzed by LDH.

1025
01:13:45,290 --> 01:13:48,480
And effectively, if you're going
to use lactate for energy--

1026
01:13:48,480 --> 01:13:51,700
so we oxidize the
lactate, generate NADH.

1027
01:13:51,700 --> 01:13:53,960
If we're going to use
it for fermentation,

1028
01:13:53,960 --> 01:14:00,930
we produce lactate, reoxidize
the NADH back to NAD+.

1029
01:14:00,930 --> 01:14:05,070
How does LDH know which
direction to go in?

1030
01:14:05,070 --> 01:14:07,650
How does any
reaction, any pathway

1031
01:14:07,650 --> 01:14:09,900
know which direction to go in?

1032
01:14:09,900 --> 01:14:11,090
Its delta G.

1033
01:14:11,090 --> 01:14:14,400
Delta G-- well, it's delta
G naught prime plus RT times

1034
01:14:14,400 --> 01:14:18,340
the log of, in this case, the
pyruvate lactate ratio times

1035
01:14:18,340 --> 01:14:22,200
the NADH/NAD+ ratio.

1036
01:14:22,200 --> 01:14:30,050
And so how oxidized or reduced
NAD+ to NADH is will determine

1037
01:14:30,050 --> 01:14:35,990
how oxidized and reduced the
pyruvate lactate ratio is.

1038
01:14:35,990 --> 01:14:39,170
In other words, this must
be true for absolutely

1039
01:14:39,170 --> 01:14:41,840
any redox pair.

1040
01:14:41,840 --> 01:14:45,380
And in general, remember
carbon oxidation is favorable.

1041
01:14:45,380 --> 01:14:48,470
And that's because
oxidizing carbon

1042
01:14:48,470 --> 01:14:51,290
to give those electrons
to something downstream,

1043
01:14:51,290 --> 01:14:54,320
ultimately oxygen, is favorable.

1044
01:14:54,320 --> 01:15:00,390
That's really what's driving
each of these pathways.

1045
01:15:00,390 --> 01:15:03,240
Now, how favorable
any of this is,

1046
01:15:03,240 --> 01:15:05,310
of course, can be quantified?

1047
01:15:05,310 --> 01:15:07,780
And if we want to know
this for this redox pair

1048
01:15:07,780 --> 01:15:10,410
or any redox pair,
of course, this

1049
01:15:10,410 --> 01:15:13,470
is related to some
equilibrium constant.

1050
01:15:13,470 --> 01:15:16,890
And we've already discussed
that we can have this term delta

1051
01:15:16,890 --> 01:15:21,750
G naught prime that is relevant
to the equilibrium constant.

1052
01:15:21,750 --> 01:15:24,330
But it's still, because delta
G determines what happens,

1053
01:15:24,330 --> 01:15:26,310
it's still that
equilibrium constant

1054
01:15:26,310 --> 01:15:29,760
plus the ratios of the reactants
and products that will really

1055
01:15:29,760 --> 01:15:32,380
determine if the
reaction happens.

1056
01:15:32,380 --> 01:15:36,510
However, it turns out it's
useful to think about--

1057
01:15:36,510 --> 01:15:39,720
when electrons can go
to donated or accepted

1058
01:15:39,720 --> 01:15:42,450
in lots of different
reactions, it's

1059
01:15:42,450 --> 01:15:44,520
useful to come up
with a term that

1060
01:15:44,520 --> 01:15:47,700
helps us know what
is the propensity

1061
01:15:47,700 --> 01:15:51,090
of an individual pair
to accept or donate

1062
01:15:51,090 --> 01:15:54,270
an electron in either direction.

1063
01:15:54,270 --> 01:15:56,985
And we have a term for this.

1064
01:15:56,985 --> 01:16:04,620
It's denoted E naught prime,
which is the standard reduction

1065
01:16:04,620 --> 01:16:13,330
potential that
basically describes

1066
01:16:13,330 --> 01:16:15,430
for a pair of molecules--

1067
01:16:15,430 --> 01:16:18,610
NADH+, NADH, pyruvate,
and lactate--

1068
01:16:18,610 --> 01:16:21,220
in an oxidation or
reduction reaction,

1069
01:16:21,220 --> 01:16:24,790
how likely is it to
give up its electrons

1070
01:16:24,790 --> 01:16:27,260
in one direction or the other.

1071
01:16:27,260 --> 01:16:32,070
And so the units
of this is volts.

1072
01:16:32,070 --> 01:16:34,860
And the standard
reduction potential

1073
01:16:34,860 --> 01:16:37,690
can be calculated as follows.

1074
01:16:37,690 --> 01:16:41,940
And of course, it's related
to the equilibrium constant

1075
01:16:41,940 --> 01:16:44,950
of a reaction.

1076
01:16:44,950 --> 01:16:48,060
And so the equilibrium
constant overreaction,

1077
01:16:48,060 --> 01:16:51,150
delta G naught prime-- related
to the equilibrium constant--

1078
01:16:51,150 --> 01:16:53,070
is this formula.

1079
01:16:53,070 --> 01:16:55,530
N is the number of
electrons transferred,

1080
01:16:55,530 --> 01:17:00,660
F is the Faraday constant,
and delta E naught prime

1081
01:17:00,660 --> 01:17:03,450
is the change in
standard reduction

1082
01:17:03,450 --> 01:17:10,230
potential from electron donation
from one pair to the next pair.

1083
01:17:10,230 --> 01:17:14,190
So if we use our lactate
pyruvate example,

1084
01:17:14,190 --> 01:17:25,610
we have lactate going to
pyruvate plus 2 electrons.

1085
01:17:25,610 --> 01:17:28,040
So that's the electron donor.

1086
01:17:28,040 --> 01:17:30,790
It's being oxidized.

1087
01:17:30,790 --> 01:17:41,770
And then you have NAD+ plus
the electrons going to NADH.

1088
01:17:41,770 --> 01:17:46,790
It's being reduced-- two
electrons, of course--

1089
01:17:46,790 --> 01:17:48,790
it's being reduced.

1090
01:17:48,790 --> 01:17:54,760
And so this has a standard
reduction potential.

1091
01:17:54,760 --> 01:18:00,140
This half reaction has a
standard reduction potential.

1092
01:18:00,140 --> 01:18:04,990
And so the difference between
these standard reduction

1093
01:18:04,990 --> 01:18:06,130
potentials--

1094
01:18:06,130 --> 01:18:10,080
that is, who receives
the electrons, delta E

1095
01:18:10,080 --> 01:18:14,590
naught primed 2 minus
delta E naught prime 1

1096
01:18:14,590 --> 01:18:19,870
gives us this change in standard
reduction potential, which

1097
01:18:19,870 --> 01:18:23,320
I can plug into
this formula, which

1098
01:18:23,320 --> 01:18:27,670
is related to the equilibrium
constant and tells me

1099
01:18:27,670 --> 01:18:31,030
which direction of
electron transfer

1100
01:18:31,030 --> 01:18:35,480
is going to be favored,
at least at equilibrium.

1101
01:18:35,480 --> 01:18:42,400
And so if this number is
related to equilibrium,

1102
01:18:42,400 --> 01:18:43,840
there's a negative here.

1103
01:18:43,840 --> 01:18:49,600
And so if this term is
positive, delta G naught prime

1104
01:18:49,600 --> 01:18:50,900
will be negative.

1105
01:18:50,900 --> 01:18:52,690
And that means that
electron transfer

1106
01:18:52,690 --> 01:18:54,880
will be favored at equilibrium.

1107
01:18:54,880 --> 01:18:57,130
If this number is
negative, that means

1108
01:18:57,130 --> 01:19:02,450
the reverse electron transfer
will be favored at equilibrium.

1109
01:19:02,450 --> 01:19:08,510
And so it stands to reason
then that electron transfer

1110
01:19:08,510 --> 01:19:21,910
from smaller standard reduction
potential to larger standard

1111
01:19:21,910 --> 01:19:26,570
reduction potentials
will be favored.

1112
01:19:26,570 --> 01:19:29,510
Hopefully that makes sense--

1113
01:19:29,510 --> 01:19:30,820
so smaller to larger.

1114
01:19:30,820 --> 01:19:35,340
Now, that could be
more negative to less

1115
01:19:35,340 --> 01:19:40,500
negative, negative to positive,
positive to more positive.

1116
01:19:40,500 --> 01:19:45,270
As long as that
delta is positive,

1117
01:19:45,270 --> 01:19:49,170
electron transfer
will be favored.

1118
01:19:49,170 --> 01:19:53,640
Now, of course, the
ratios still matter.

1119
01:19:53,640 --> 01:19:55,980
But this standard
reduction potential

1120
01:19:55,980 --> 01:19:58,860
is useful because
it can help us know

1121
01:19:58,860 --> 01:20:04,590
which direction transfer wants
to occur between any redox

1122
01:20:04,590 --> 01:20:07,790
pairs at equilibrium.

1123
01:20:07,790 --> 01:20:12,380
And so recognizing
this, you must

1124
01:20:12,380 --> 01:20:16,730
know that carbon oxidation
electron transfer in general

1125
01:20:16,730 --> 01:20:23,870
is going to be favored
to NAD to make NADH.

1126
01:20:23,870 --> 01:20:28,490
And in general, that
NADH electron transfer

1127
01:20:28,490 --> 01:20:30,890
is going to be
favored to oxygen.

1128
01:20:30,890 --> 01:20:34,460
And it's coupling those
favorable electron transfers

1129
01:20:34,460 --> 01:20:37,730
that ultimately is
allowing the system

1130
01:20:37,730 --> 01:20:44,180
to use oxidation and
reduction reactions to drive

1131
01:20:44,180 --> 01:20:46,680
these various pathways.

1132
01:20:46,680 --> 01:20:51,830
And that energy release
from these electron transfer

1133
01:20:51,830 --> 01:20:56,180
reactions can be used to
make ATP and do other work,

1134
01:20:56,180 --> 01:21:01,690
as we will talk about in great
detail in the next lecture.