Glycogen Synthesis and Degradation

glucose homeostasis
is maintained by
making what, and
by making and
degrading what

glucose, glycogen

glycogen

storage form of glucose in all
organisms except plants (which use starch)

Glycogen is a polymer of which-linked glucose subunits, with
which-linked branch points every 8-12 residues

(α1→4), (α1→6)

metabolized

glycogen can be what to liberate energy rapidly

oxygen

glycogen can be metabolized to liberate energy rapidly (as in active
muscles) and it can happen without the need for what (as in red blood
cells on their way back to the lungs)

cytoplasmic granules

Glycogen is stored where that may contain 50,000 glucose
residues.

A cell can only store about a how much of glycogen

1 day

In muscles cells, glycogen will be broken down to provide glucose
directly to those cells when they are what

active

which glycogen is broken down to meet the energy needs of the
muscle during heavy use

Muscle

which glycogen is broken down to meet the energy needs of other
cells of the body and to feed the brain overnight.

Liver

homeostasis

In the liver, the rates of glycolysis and gluconeogenesis are
adjusted to maintain a constant blood glucose level (glucose
what) between meals

glycogen phosphorylase

What catalyzes phosphorolytic cleavage at the free
ends of glycogen chains.

How many glucose is cleaved off in the form of glucose 1-phosphate

1

Glycogen phosphorylase can only cleave which bonds

α-1,4-glycosidic

A what enzyme shifts a small
oligosaccharide from the free end to a
nearby chain, thereby making those
glucoses accessible to the phosphorylase

transferase

A what enzyme (α-1,6-glucosidase)
cleaves the α-1,6 bond at the branch point,
releasing a free glucose

debranching

Phosphoglucomutase

What converts glucose 1-phosphate into glucose 6-
phosphate via a glucose 1,6-bisphosphate intermediate by ‘swapping’
phosphates with a phosphorylated serine residue on the enzyme

glucose 6-phosphate

In skeletal muscle, what enters glycolysis to
make energy directly

well-fed

The postprandial or what state occurs shortly after eating and
lasts 3 - 5 hours

insulin

In the ‘well-fed’ state, glycogen stores are replenished

Blood glucose levels rise and stimulate what release by b cells of the pancreas

In the ‘well-fed’ state, glycogen stores are replenished

In the liver and muscle cells, insulin promotes glycogenesis to do what to glucose
levels in the blood

decrease

sources of glucose 6-phosphate:
- hexokinase creates glucose 6-phosphate from glucose in
the first reaction of what

glycolysis

disaccharides

sources of glucose 6-phosphate:
- dietary starch and what (sucrose, lactose, fructose)
are metabolized to glucose and to other monosaccharides
that can be converted to glucose 6-phosphate

lactate

sources of glucose 6-phosphate:
- what from muscle is taken up by the liver and converted to
glucose 6-phosphate by gluconeogenesis (Cori cycle)

glucose 1-phosphate

phosphoglucomutase = converts glucose 6-phosphate to what

glucose 1-phosphate

UDP-glucose pyrophosphorylase converts what to UDP-glucose

UDP-glucose

Glucose residues are added to an existing glycogen chain one
at a time in the form of what

glycogen synthase
catalyzes the transfer of
the glucose residue from
UDP-glucose to a free end
of a branched glycogen
molecule, forming a what linkage

(α1⟶ 4)

Glycogen synthase can only
synthesize which-linkages

α-1,4

A branchingenzyme generates
branches by cleaving an α-1,4-
linkage and taking a block of
approximately how many glucoses
and moving it and creating an
α-1,6-linkage

7

primer

glycogen synthase
requires a what

glycogenin

an enzyme dimer that
catalyzes the transfer of
the initial glucose
residues to itself

Only how many ATP are required to incorporate glucose into glycogen

2

The complete oxidation of one glucose derived from glycogen
yields how many molecules of ATP

30

glycogen phosphorylase

what is the regulated enzyme in glycogen degradatio

glycogen phosphorylase has two forms:
– glycogen phosphorylase a = what

active

glycogen phosphorylase has two forms:
– glycogen phosphorylase b = what

inactive

phosphorylation

glycogen phosphorylase is regulated allosterically by small molecules, and
by covalent modification (what). These events shift the
equilibrium between the inactive and active states of the enzyme

To complicate things further, there are two phosphorylase isozymes, one
found in muscle, one found in liver and they are regulated how

differently

Muscle phosphorylase is in which form until glucose is needed

b

When energy is needed:
what accumulates in vigorously contracting muscle
– what binds to an allosteric site and activates muscle phosphorylase to
speed up glucose release from glycogen

AMP

When energy is not needed:
what blocks the AMP allosteric site, and inhibits phosphorylase
Glucose 6-phosphate binds an allosteric site and inhibits phosphorylase

ATP

When energy is not needed:
ATP blocks the AMP allosteric site, and inhibits phosphorylase
Glucose 6-phosphate binds an allosteric site and does what to phosphorylase

inhibits

Recall that key enzymes in glycolysis are also activated by AMP and inhibited by ATP
à in this way, a which energy state causes glucose to be liberated by glycogenolysis
and used to make energy by glycolysis

low

Liver phosphorylase is usually in which form – thus, liver
phosphorylase is prepared to generate glucose unless signaled otherwise

a

Liver phosphorylase is or is not regulated by energy charge (ATP vs AMP)

is not

Glucose is a what regulator of liver phosphorylase, facilitating the transition
from the R state to the T state, shifting it too a less active state
(don’t make glucose if we have enough)

negative

Glycogen phosphorylase is a what

dimer

Phosphorylation of Ser14 in which form causes a conformational change such
that α helices that partially block the active site in the b form are moved and
the enzyme becomes fully active

a

Phosphorylase T state

b form

Phosphorylase R state

a form

kinase

phosphorylase what is the enzyme responsible for phosphorylation of
glycogen phosphorylase at Ser 14

contraction

Ca2+ is released during muscle what

phosphorylase kinase activity is activated by an what in Ca2+ levels
within muscle cells

decrease

phosphorylase kinase activity is activated by the hormones glucagon

in liver

phosphorylase kinase activity is activated by the hormones epinephrine

in muscles

Most of the pancreas is made of endocrine cells that secrete
enzymes into the small intestine during digestion
It also contains about a million islet cells
a cells secrete the hormone what

glucagon

Most of the pancreas is made of endocrine cells that secrete
enzymes into the small intestine during digestion
It also contains about a million islet cells
b cells secrete the hormone what

insulin

hyperglycemic

glucagon – 29 amino acid hormone that is a
potent what agent – one molecule
of glucagon can cause the release of 100
million glucose molecules into the blood

breakdown of glycogen in the liver is
regulated by glucagon from the what

pancreas

epinephrine

Glycogen breakdown in muscle is regulated by what (adrenaline)
secreted by the adrenal glands

glycogen synthase also has two forms:
– glycogen synthase a = what

unphosphorylated and catalytically active

glycogen synthase also has two forms:
– glycogen synthase b = what

phosphorylated and inactive unless glucose 6-phosphate is present

Notice the key difference:
- glycogen phosphorylase is what when it is phosphorylated

active

Notice the key difference:
- glycogen synthase is what when it is phosphorylated

inactive

glycogen synthase kinase 3 (GSK3)

what = catalyzes the phosphorylation of glycogen synthase a

glycogen synthase kinase
3 (GSK3) phosphorylates
glycogen synthase at three
serines, doing what to it

inactivating

PP1 (protein phosphatase 1)

glycogen synthase kinase 3 (GSK3) phosphorylates glycogen synthase at three serines, inactivating it

these phosphates are removed by what, activating glycogen synthase

glucagon and epinephrine signaling does what PP1

inhibit

glucagon and epinephrine signaling inhibit PP1
this keeps glycogen synthase in the phosphorylated, catalytically what state

inactive

glucose 6-phosphate (G6P) does what glycogen synthase

stimulates

glucose 6-phosphate binds on allosteric site on glycogen synthase b which causes a conformational change that makes it a better substrate for PP1 (thereby what)

activating it

insulin

51 amino acid hormone made of two disulfide-bonded
chains that lowers blood glucose levels

glycogenesis

insulin – 51 amino acid hormone made of two disulfide-bonded
chains that lowers blood glucose levels by
- increasing expression of glucose transporters in cells
- promoting glycolysis
- promoting what

GLUT4 Km similar to [glucose] in blood means this transporter is usually saturated after a meal
- levels regulated by what

insulin

glycogen synthase kinase 3 (GSK3)

which enzyme responds to insulin signaling

insulin signaling inactivates what and activates what

GSK3, PP1

insulin signaling inactivates GSK3 and activates PP1 this keeps glycogen synthase in the unphosphorylated, catalytically what state this results in glycogen synthesis

active

diabetes mellitus

a relatively common disease affecting ~9% of the U.S. population

stems from an autoimmune destruction of pancreatic
β cells, resulting in the inability to produce sufficient insulin
- begins early in life
- responds to insulin injection

type 1 diabetes

group of diseases in which insulin is made, but cells
no longer respond to it (insulin resistance)
- slower to develop and typically in obese adults
- responds to insulin injection

type 2 diabetes

metabolic syndrome

what = the stage preceding type 2 diabetes