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PROFESSOR: In this
session, we're

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going to be looking at
carbohydrate biosynthesis.

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Please look at Storyboard 29.

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Looking at Panel A, the
next set of pathways

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on which we're going
to focus concerns

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carbohydrate biosynthesis.

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First, we're going to look at
the pathway by which glycogen

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is made.

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As you know, glycogen is the
polymeric form of glucose

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that's very readily available
for energy production.

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The second pathway
is gluconeogenesis.

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The organs that utilize
glucose as their metabolic fuel

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prefer to have glucose at a
concentration of about 100

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milligrams per
deciliter in the blood.

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The challenge
comes from the fact

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that we eat only sporadically,
and thus, levels of glucose

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will go up and down
depending upon the time that

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has passed since our last meal.

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When glucose levels
drop, gluconeogenesis

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is the pathway that's activated.

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00:01:10,160 --> 00:01:12,590
It takes non-carbohydrate
precursors,

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converts them to glucose,
and then secretes the glucose

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into the blood,
ultimately to help

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maintain a constant
glucose concentration.

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00:01:20,360 --> 00:01:22,700
Looking at Panel
B, our first topic

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00:01:22,700 --> 00:01:26,450
is the synthesis of glycogen.
If you look back at my first two

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lectures, I describe the
structure of glycogen,

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which is also shown here.

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00:01:30,939 --> 00:01:32,480
The piece of glycogen
that I've shown

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consists of a linear chain of
glucose molecules connected

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together through
the 1 and 4 carbons.

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00:01:37,960 --> 00:01:41,510
Chemically, we call this
an alpha 1, 4 linkage.

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00:01:41,510 --> 00:01:43,130
To the left of the
glycogen molecule

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is the non-reducing
end and to the right

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is the reducing end, which is
connected by a tyrosine residue

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00:01:49,430 --> 00:01:51,650
to a protein called glycogenin.

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00:01:51,650 --> 00:01:54,830
Glycogenin is a variant of
the glycogen synthase enzyme

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00:01:54,830 --> 00:01:56,410
we'll talk about later.

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00:01:56,410 --> 00:01:58,010
Glycogenin has the
property that it

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00:01:58,010 --> 00:02:00,560
can synthesize a
polymeric glucose

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00:02:00,560 --> 00:02:03,290
chain, such as the
one shown, to boot up

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00:02:03,290 --> 00:02:05,110
the synthesis of glycogen.

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00:02:05,110 --> 00:02:08,660
In effect, glycogenin
forms a primer molecule

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00:02:08,660 --> 00:02:10,580
such as the one
shown that provides

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a non-reducing end that can be
extended by its sister enzyme,

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glycogen synthase.

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While I've drawn
a linear glucose,

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I want you to keep
in mind, the branches

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off of the six carbon of
the glucoses in the chain

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are possible.

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As I mentioned earlier, glycogen
is designed for fast breakdown.

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Its glucose units will quickly
enter the pathway of glycolysis

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and generate ATPs in
a manner of seconds.

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00:02:35,030 --> 00:02:37,910
Let's now look at Panel
C. It's useful to review

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the biochemical steps by
which glycogen is broken down

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because the exact same
intermediates appear

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in the reverse order in
the synthesis of glycogen.

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The key enzyme for
glycogen breakdown,

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00:02:48,890 --> 00:02:52,520
or glycogenolysis, is
glycogen phosphorylase.

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00:02:52,520 --> 00:02:55,790
Glycogen phosphorylase
progressively will nip off

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00:02:55,790 --> 00:02:57,470
the non-reducing end--

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00:02:57,470 --> 00:02:59,480
that is the left-most
sugar as shown--

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00:02:59,480 --> 00:03:02,510
producing oxonium
ion intermediate.

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00:03:02,510 --> 00:03:04,520
And as we saw in
my first lecture,

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glycogen phosphorylase
stereospecifically adds

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00:03:07,820 --> 00:03:09,890
inorganic phosphate
to the bottom face--

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00:03:09,890 --> 00:03:12,590
that is the alpha face
of the oxonium ion--

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to give glucose 1-phosphate
with this stereochemistry shown.

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Once again, these
same intermediates

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are going to appear in
the synthesis of glycogen.

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00:03:22,020 --> 00:03:23,990
Now let's take a
look at the way that

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glucose 1-phosphate interfaces
with the other biosynthetic

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00:03:27,500 --> 00:03:29,730
and catabolic pathways.

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00:03:29,730 --> 00:03:32,090
Let's look at Panel
D. This metabolic map

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shows glycogen in the
lower right-hand corner.

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We can see how glycogenolosis
results in glycogen breakdown

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00:03:38,780 --> 00:03:42,020
to glucose 1-phosphate, and
in the reverse direction,

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00:03:42,020 --> 00:03:45,020
we can see how glucose
1-phosphate can be used to make

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glycogen by way of two enzymes--

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UDP Glucose Pyrophosphorylase,
UGP, and Glycogen Synthase, GS.

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00:03:55,610 --> 00:03:57,950
Let's look a little
deeper at other pathways

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00:03:57,950 --> 00:04:00,920
with which glucose 1
phosphate interfaces.

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00:04:00,920 --> 00:04:03,260
This schematic shows
that glucose 1-phosphate

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00:04:03,260 --> 00:04:05,270
can be converted to
glucose 6-phosphate

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00:04:05,270 --> 00:04:08,480
by phosphoglucomutase, PGM.

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00:04:08,480 --> 00:04:10,970
In this case, the phosphate
is moved from the 1 carbon

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00:04:10,970 --> 00:04:14,270
to the 6 carbon of
the glucose moiety.

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00:04:14,270 --> 00:04:16,339
The opposite
reaction also occurs.

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That is, if you have
glucose 6-phosphate,

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phosphoglucomutase will convert
it to glucose 1-phosphate.

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Glucose 6-phosphate is an
intermediate in glycolysis,

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00:04:26,150 --> 00:04:28,520
gluconeogenesis-- which is
the next pathway we're going

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00:04:28,520 --> 00:04:29,300
to look at--

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00:04:29,300 --> 00:04:32,420
and another future pathway,
the pentose phosphate pathway.

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All of this shows us
that glucose 6-phosphate

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is a crossroads and one of the
branches that leads from it

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00:04:38,450 --> 00:04:41,990
and it is by way of
glucose 1-phosphate.

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Let's imagine a scenario
in which we eat a meal.

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Glucose appears in
the blood as shown.

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It is taken into the cell.

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The enzymes hexokinase
or glucokinase

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will phosphorylate the glucose
into glucose 6-phosphate.

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00:04:55,700 --> 00:04:57,980
If the glucose is not
needed for glycolysis

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or the other pathways
that I mentioned,

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00:04:59,840 --> 00:05:02,780
phosphoglucomutase will
convert the glucose

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00:05:02,780 --> 00:05:04,880
6-phosphate to
glucose 1-phosphate,

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and then in the pathway
of glycogen synthesis,

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glucose 1-phosphate will be
polymerized into glycogen

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for energy storage.

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At this point, let's turn
to Storyboard 30 and look

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00:05:15,290 --> 00:05:18,860
at Panel A. Now
let's take a look

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00:05:18,860 --> 00:05:21,560
at the detail pathway by
which glucose 1-phosphate is

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00:05:21,560 --> 00:05:23,940
converted to
glycogen. At the left

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00:05:23,940 --> 00:05:26,420
is the structure of
glucose 1-phosphate.

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00:05:26,420 --> 00:05:30,650
The first enzyme involved is
UDP Glucose Pyrophosphorylase,

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00:05:30,650 --> 00:05:32,120
or UGP.

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00:05:32,120 --> 00:05:33,860
The second substrate
in this reaction

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is UTP, uridine triphosphate.

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00:05:37,100 --> 00:05:39,710
The UDP Glucose
Pyrophosphorylase

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00:05:39,710 --> 00:05:42,140
catalyzes attack
by the phosphate

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00:05:42,140 --> 00:05:45,140
on the 1 carbon of
glucose 1-phosphate

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00:05:45,140 --> 00:05:47,630
on the alpha phosphorus of UTP.

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00:05:47,630 --> 00:05:52,100
The two products are
pyrophosphate and UDP glucose.

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00:05:52,100 --> 00:05:54,890
The reaction is made
thermodynamically irreversible

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00:05:54,890 --> 00:05:58,910
by hydrolysis of pyrophosphate
by inorganic pyrophosphatase

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into two molecules of
inorganic phosphate.

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00:06:01,770 --> 00:06:04,880
The UDP glucose is the
substrate for the next enzyme

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00:06:04,880 --> 00:06:07,640
in the sequenced
glycogen synthase.

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00:06:07,640 --> 00:06:09,740
I'm going to divide
the glycogen synthase

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reaction into two parts.

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00:06:12,030 --> 00:06:13,970
In the first, we see
cleavage of the bond

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between the 1 carbon
of the glucose

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00:06:15,950 --> 00:06:18,770
and the beta
phosphate of the UDP.

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This reaction liberates the UDP
and generates the oxonium ions

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shown in the brackets.

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00:06:25,050 --> 00:06:28,940
Structurally, this oxonium
ion is the same intermediate

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00:06:28,940 --> 00:06:31,700
we saw in glycogen
breakdown, but here, we're

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00:06:31,700 --> 00:06:35,310
using it as a
biosynthetic reagent.

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00:06:35,310 --> 00:06:37,590
Let's look at Panel
B. In this panel,

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00:06:37,590 --> 00:06:40,740
we continue the glycogen
synthase reaction.

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In Panel A, we generated
the oxonium ion

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00:06:43,200 --> 00:06:47,250
of glucose, which is shown here,
in Panel B in the lower left.

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Glycogen synthase activates
the hydroxyl group

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on the 4 carbon of the
terminal sugar residue.

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That is the sugar on
the non-reducing end.

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The oxygen on the non-reducing
sugar residue of glycogen

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then attacks the bottom
face of the oxonium ion

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00:07:03,300 --> 00:07:06,480
to give rise to a glycogen
unit that has been extended

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by one glucose residue.

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I have put an asterisk
on the 6 carbon

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of the glucose residue that's
been added to the growing

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glycogen chain.