L9 - Glycogen Metabolism

Glycogen is____; function in muscle vs liver

excess glucose stored in polymeric form; energy in muscle, storage in liver

Glycogen avoids

osmotic pressure

β-particles vs α-granules

~55,000 residues; protein-rich granules of 20-40 clustered β-particles

Bond type of glycogen chain:

Bond type of glycogen branch point:

(α1→4) glycosidic bonds; (α1→6) glycosidic bonds

Glycogenolysis -

breakdown of glycogen

Glycogenesis -

making glycogen

Glycogen phosphorylase - catalyze the phosphorolytic cleavage of

non-reducing end of glycogen chains

• A form is active

• B form is inactive

Needs P_i

Phosphorolytic cleavage of glycogen yields

glucose 1-phosphate

Glycogen phosphorylase is/is not regulated

IS

Debranching enzyme

Once glycogen has been reduced to 4 glucose on one branch, it will act as a transferase and transfer 3 of the 4 glucose onto the linear chain onto another linear chain on the non-reducing end and act as a glucosidase to release the remaining (α1→6) glucose (not G1P).

Phosphoglucomutase catalyzes

glucose 1-phosphate into glucose 6-phosphate

• In order to use it in other pathways

• Saves 1 ATP for glycolysis and increases the net ATP production to 3 (Bc hexokinase needs ATP)

• Primarily in muscle (think energy needs)

Reversible

In skeletal muscles, glucose 6-phosphate enters; What about the liver?

glycolysis; G6P enters gluconeogenesis via G6Phatase to replenish blood glucose

In allosteric regulation of glycogen phosphorylase

• Ca2+ is a signal for muscle contraction. Binds to and activates phosphorylase b kinase

• Amp accumulates in vigorously contracting muscle. Binds to and activates phosphorylase to speed up glucose 1-phosphate release from glycogen

• ATP blocks the allosteric site, inactivating phosphorylase

In hormonal regulation of glycogen phosphorylase

Epinephrine (from vigorous muscle activity) and glucagon (in the liver) trigger phosphorylation of phosphorylase b, converting it to phosphorylase a

Two forms of glycogen phosphorylase

Glycogen phosphorylase a is active, while glycogen phosphorylase b is much less active

Phosphorylase b kinase is a target of

PKA

Steps of glycogen phosphorylase regulation starting from epinephrine and glucagon

Both cause a G-protein cascade activating adenylyl cyclase, which creates cAMP that activates PKA, which activates phosphorylase b kinase, which converts glycogen phosphorylase b to glycogen phosphorylase a, which can then break down glycogen to G1P

AMP directly acts on

glycogen phosphorylase a (activation)

Protein Phosphatase 1 (PP1) dephosphorylates

phosphorylase a to phosphorylase b

PP1 is under the control of

insulin

Glycogenin

a dimer that acts as a primer on which new glycogen chains are assembled and the enzyme that catalyzes their assembly

To build glycogen we need; What enzyme and substrates/products?

activated sugar nucleotides (UDP-glucose); UTP + G1P turns into UDP-glucose + PP_i via UDP-glucose pyrophosphorylase

Glycogen synthase

Catalyzes transfer of glucose from UDP glucose to growing glycogen (α1→4) from the non-reducing end; Also has a and b form (active/inactive)

Sugar nucleotide compounds are anomeric carbon of a sugar activated by

the attachment of a nucleotide through phosphate extra linkage.

UDP-glucose pyrophosphorylase catalyzes

• UTP + Glucose 1-phosphate -> UDP-glucose + PPi

• Glucose 1-phosphate is from PPP

Phosphoglucomutase makes G6P to G1P

Branching enzymes =

amylo (1→4) to (1→6) transglycosylase

Branching enzyme lifts up a chain and puts them into an

a1→6 branch point of a previous molecule (From the 4th glucose, imagine debranching enzyme but reverse)

Insulin enhances PP1 to

phosphorylate Glycogen synthase b to a

Insulin inhibits _______ while enhancing ______

GSK3, which keeps glycogen synthase dephosphorylated; PP1

Glucose 6-phosphate that enhances

PP1 to convert glycogen synthase b to a

Glucagon and epinephrine inhibits PP1 to

convert glycogen synthase b to a

Skeletal muscle uses its own stored glycogen only for ________ because

its own needs; it can undergo very large changes in its demand for ATP

Skeletal muscle lacks the enzymatic machinery for

gluconeogenesis

Liver vs muscle during epinephrine release

Glucose production/release vs glucose consumption for energy

Glucose and glycogen pathway

In the liver