Glycogen Metabolism

Question 1

Glycogen is a branched-chain ____________ of glucose stored in the liver and skeletal muscle as cytosolic ________.

_________ glycogen stores regulate blood glucose

__________ glycogen stores serve as a fuel reservoir

Answer 1

Homopolymer; granules

Liver

Muscle

Question 2

Glycogen chains are linked together by ______ glycosidic bonds, with branch points every 8-10 residues that are connected by _____ glycosidic bonds.

Answer 2

Alpha 1,4

Alpha 1,6

Question 3

The non-reducing ends of glycogen have free ________ groups at C4, and this is where glucose will extend from during glycogenesis

Answer 3

Hydroxyl

Question 4

The reducing ends of glycogen are bound to a protein called __________ which is at the core of the granule

Answer 4

Glycogenin

Question 5

What serves as the primer for glycogen synthesis?

Answer 5

Glycogenin

Question 6

What are the 3 key steps of glycogenesis?

Answer 6

Trapping glucose

Elongation

Branching

Question 7

What is the rate limiting step of glycogenesis?

Answer 7

Transfer of UDP-glucose onto the non-reducing end of the glycogen chain

Enzyme = glycogen synthase

Question 8

What enzyme is required for the branching process of glycogenesis?

Answer 8

Glucosyl (4:6) transferase

Question 9

What are the 2 major steps of glycogenolysis?

Answer 9

Chain shortening

Branch transfer

Question 10

What is the rate limiting step of glycogenolysis?

Answer 10

Cleavage of glucose as G1P from the non-reducing end of glycogen chain

Enzyme = glycogen phosphorylase (requires PLP aka vit. B6)

Question 11

What enzyme catalyzes branch transfer in glycogenolysis when phosphorolysis reaches within 4 residues of a branch point? What does this generate?

Answer 11

Debranching enzyme aka alpha-1,6 glucosidase

Releases free glucose, but the ratio of G1P to Glucose is 10:1

Question 12

Glycogenolysis generates G1P, what is its fate in the liver?

Answer 12

An epimerase converts it to G6P and glucose 6 phosphatase can then convert it to glucose that then enters the blood

Question 13

Glycogenolysis generates G1P, what is its fate in the muscle?

Answer 13

Myocytes lack G6-phosphatase, so once G1P becomes G6P, it cannot be hydrolyzed to glucose. It will be used directly to generate energy via glycolysis and TCA

Question 14

Compare the active/inactive forms of glycogen synthase in terms of phosphorylation

Answer 14

Phosphorylated glycogen synthase = inactive

Dephosphorylated glycogen synthase = active

Question 15

In glycogen metabolism, insulin positively regulates the protein ___________ enzyme in order to activate glycogen synthase, while glucagon/epinephrine positively regulate ________ in order to deactivate glycogen synthase

Answer 15

Phosphatase (remove phosphate to activate!)

PKA (via cAMP)

Question 16

In glycogen metabolism, insulin positively regulates the protein ___________ enzyme in order to activate glycogen phosphorylase, while glucagon/epinephrine positively regulate ________ in order to deactivate glycogen phosphorylase

Answer 16

Phosphatase (dephosphorylated glycogen phosphorylase is inactive)

Phosphorylase kinase (via cAMP)

Question 17

Rabson-Mendenhall syndrome occurs when both alleles of the _____ gene are defective. It is characterized by growth retardation, dysmorphism, lack of subQ fat, acanthosis nigricans, enlarged genitalia, dysplastic dentition, hirsutism, coarse facial features, and most notably: constant hyperglycermia, ketoacidosis, and hyperinsulinemia.

Answer 17

INSR (it is a genetic disorder of the insulin receptor)

Question 18

Another genetic disorder of the insulin receptor involves marked insulin resistance, severe growth retardation, hypertrichosis, and diminished adipose tissue. It is generally more severe than Rabson-Mendenhall syndrome, with spontaneous abortion or very early death likely

Answer 18

Donohue syndrome

Question 19

When blood glucose is low, glucagon is released by the _____ cells of the pancreas, and binds to a ______ on hepatocytes in order to activate a signaling cascade to prevent glycogen synthesis

Answer 19

Alpha; GPCR

Question 20

True or false: glucose inhibits glycogen phosphorylase throughout the body

Answer 20

False, glucose inhibits glycogen phosphorylase in the LIVER only

Question 21

The following would result from a deficiency in what enzyme:

Inability to store glucose as glycogen, resulting in high dependence on dietary glucose, high susceptibility to hypoglycemia when fasting, frequent muscle cramping

Answer 21

Glycogen synthase

Question 22

The following would result from a deficiency in what enzyme:

Longer chain glycogen with fewer branches, manifesting as hepatosplenomegaly, cirrhosis, and death within 5 years of birth

Answer 22

Glycosyl 4:6 transferase (Anderson disease)

Question 23

Liver and muscle isoforms of glycogen phosphorylase are products of 2 separate genes on chr. 14 and 11, and have different sensitivities to regulatory molecules. Both are activated by phosphorylation and allosterically inhibited by ____ and _____

Answer 23

ATP; G6P

Question 24

Mutations in the liver isoform of glycogen phosphorylase cause _______ disease, where it is inactivated by free glucose

Mutations in the muscle isoform of glycogen phosphorylase cause _______ disease, where it is allosterically activated by AMP, Ca-Calmodulin complex, and G-actin

Answer 24

Hers

McArdle

Question 25

The following would result from a deficiency in what enzyme:

Patients possess glycerol molecules with large number of short branches; manifests as light hypoglycemia and hepatomegaly

Answer 25

Debranching enzyme (alpha 1,6 glucosidase) aka Cori disease

Question 26

The following would result from a deficiency in what enzyme:

Inability to supply muscles with sufficient glucose, so patients suffer from fatigue, severe muscle cramping, and myoglobinuria. Tolerable by limiting strenuous physical activity

Answer 26

Glycogen phosphorylase (aka McArdle disease)