Exam 2 Glycogen review

Question 1

What is the advantage of glycogen breakdown by phosophorolysis compared to hydrolysis?

Answer 1

In phosphorylation, glycogen can be broken down without ATP, and the concentration of Pi is high enough to drive the reaction in a favorable direction.

Question 2

2. Describe the significance of glycogenolysis in liver vs. muscle.

Answer 2

Glycogenolysis in the liver produces glucose for extra hepatic tissues (mainly the brain.)

In muscle, the glycogen is broken down to G1P–> G6P which is then directly used for glycolysis ( since skeletal muscle doesn’t have glucose 6 phosphatase

Question 3

Describe how glucose-1-phosphate is converted into glucose-6-phosphate.

Answer 3

G1P + EnZ-(P) ↔ EnZ + G1,6-bP ↔ EnZ-(P) + G6P

EnZ= Phosphoglucomutase

Question 4

. Describe the phosphorylation mediated regulation of enzyme activity.

Answer 4

Phosphorylation of enzymes can convert them to active or inactive states, serving as a mechanism for mediation

Question 5

Name the two hormones that are involved in triggering glycogenolysis and describe their specificity.

Answer 5

Glucagon: Secreted by pancreas as a result of low blood sugar levels. Binds to hepatocyte receptors in the membrane of liver cells.

Epinephrine: Released from adrenal medulla. Binds to muscle cell receptors (or hepatocyte receptors in liver) to regulate the pathway directly. Can also bind to α-adrenergic receptors and trigger glycogenolysis through IP3 and DAG

Question 6

Describe the mechanism by which PKA is activated.

Answer 6

Epinephrine or glucagon bind to receptors which results in activation of adenylate cyclase, which forms cAMP.

cAMP binds to PKA, which releases the regulatory subunit, activating the catalytic subunit.

Question 7

. Describe the glycogenolysis cascade, and discuss the kinases that are involved in the pathway.

Answer 7

.) Epinephrine or Glucagon bind to receptors, activating adenylate cyclase.

2. ) Adenylate cyclase catalyzes ATP to cAMP.
3. ) cAMP causes Protein Kinase A (PKA) to separate its R and C subunits.
4. ) The C subunits activate phosphorylase kinase by phosphorylation.
5. ) Phosphorylase kinase activates glycogen phosphorylase by phosphorylation.
6. ) Glycogen phosphorylase is an up-regulator of glycogenolysis.

Question 8

Describe the role of calcium in glycogenolysis, especially with reference to the neuromuscular stimulus

Answer 8

One of the subunits of phosphorylase kinase is similar to calmodulin, which binds Ca2+.

Binding to Ca2+ induces a conformal change which activates phosphorylase kinase.

During muscle contraction (depolarization), Ca2+ release is promoted, which positively affects phophorylase kinase into its active form.

Question 9

Describe the activation of the alpha-adrenergic receptor and the associated cascade of biochemical events.

Answer 9

1. ) Epinepherine → α-adrenergic receptor (G-protein)→ phospholipase C
2. ) Phospholipase C catalyzes PIP2 → IP3 or DAG.

3.) IP3 → Ca2+ → Phosphorylase Kinase-(P)
↓
3a.) DAG → PKC → Glycogen Synthase-(P)

Question 10

Describe the role of protein phosphatase inhibitor (PPI-1) during glycogenolysis.

Answer 10

PP1 removes Pi from phosphorylase kinase and phosphorylase-A (Inhibiting glycogenolysis)

PPI binds PP1 to regulate it

Question 11

Describe the fight or flight response.

Answer 11

The release of epinephrine from the adrenal medulla in response to neural signals (stress, danger, etc.)

Question 12

12.Describe the role of AMP in muscle.

Answer 12

AMP is a positive affector that stabilizes glycogen phosphorylase in the relaxed (active) state.

Question 13

. Describe how UDP-glucose is formed.

Answer 13

G1P + UTP → UDPG + Ppi
(G1P uridylyl transferase)

The energy of the phospho-glycidic bond in UDPG is used by glycogen synthase to make glycogen.

Question 14

How are α-1-6 branches in glycogen formed?

Answer 14

Glucan transferase (branching enzyme) transfers a fragment of 6-7 residues from the terminal end of the chain to an internal glucose residue at the C6 position.

Question 15

.What is glycogenin?

Answer 15

A protein that serves as the primer required by glycogen synthase since it can normally only elongate existing glucose chains.

Question 16

.Describe the three major allosteric effectors and its effect on glycogen synthase-b.

Answer 16

AMP (positive affector)

ATP, G6P (negative affectors)

Question 17

17.Describe the properties and role of glucose-6-phosphatase in glycogen metabolism

Answer 17

G6P-ase dephosphorylates G6P to glucose. It is not present in skeletal muscle

Question 18

Describe how a futile cycle of glycogenolysis and glycogen synthesis (i.e. operating at the same time) is prevented.

Answer 18

Phosphorylation has the dual effect of activating glycogen phosphorylase which up regulates glycogenolysis and inactivates glycogen synthase which down-regulates glycogen synthesis.

Question 19

Describe very briefly the mode of action of α-adrenergic and β-adrenergic hormones.

Answer 19

The hormone binds to the receptor, which causes a nearby G-protein to interact with the receptor.

After a replacement of GDP for GTP, a subunit of the G-protein disassociates, and then activates adenylate cyclase.

The adenylate cyclase converts ATP to cAMP.

When the GTP is hydrolyzed to GDP, the system returns to its resting state.

Question 20

What are heterotrimeric proteins?

Answer 20

Proteins with 3 different subunits. (α, β, γ)

Question 21

.Briefly describe how protein kinase A (PKA) is activated.

Answer 21

PKA is activated when cAMP binds to its R subunits, separating them, and leaving the C subunit available to participate in other reactions.

Question 22

What are the products that are formed by the action of phospholipase C?

Answer 22

PLC hydrolyses PIP2 into IP3 and DAG

Question 23

23.Describe the control of blood glucose level by the hormones.

Answer 23

Insulin increases uptake of glucose from the blood (anabolic hormone).

Glucagon induces catabolic effects.

Question 24

Pompe’s disease

Answer 24

Lysosomal α-glycosidase deficiency

Question 25

coris disease

Answer 25

defects in debranching enzyme

Question 26

McArdle’s disease

Answer 26

skeletal muscle phosphorylase deficiency

Question 27

Andersons disease

Answer 27

defect in branching enzyme

Question 28

von Gierkes disease

Answer 28

lack of g6P ase
G6P is made but can’t leave the ER → h​ypoglycemia
■ does not affect muscle

Question 29

You would advise the patient to NOT perform heavy exercise in patients with
which disease?

Answer 29

McArdle’s

Question 30

Can Von Gierke’s patients carry out gluconeogenesis normally? If not, explain why?

Answer 30

The patients would have the ability to create glucose­6­phosphate, but they
would not be able to cleave the phosphate group off while in the ER.

Question 31

Which of the tissues (liver or muscle) would contain more total glycogen or glycogen per
gram of tissue?

Answer 31

Skeletal muscle (400g vs 100g in Liver)
○ However, liver contains more per gram of tissue

Question 32

29. What is/are the physiological advangtage(s) of having branched glycogen as opposed to
    linear glycogen in mammals?

Answer 32

The body is able to start the breakdown of glycogen at many terminal ends and
thus get the benefits of energy release at a much quicker pace than if the
glycogen molecule was linear and had only one point of glycogen breakdown.

Question 33

Type I diabetes

Answer 33

Insulin is not made, so glucose is not taken up from blood into cells, and
blood glucose levels remain high.
■ The insulin/glucagon ratio is low. So glucagon activity increases glycogen
metabolism, releasing more glucose into the blood.
■ Low insulin/glucagon ratio also increases gluconeogenesis, which results
in more glucose being produced and released into the blood, further
increasing the blood glucose level.

Question 34

Type II diabetes

Answer 34

insulin levels are normal, but the insulin receptor is less responsive to
insulin. Since insulin cannot bind to its receptor, glucose uptake from
blood into cells is impaired, resulting in high blood glucose.

Question 35

Type I diabetes can be better controlled by insulin administration (true or false)?

Answer 35

true

Question 36

Can we come up with a hypothesis as to why type 2 diabetics are obese

Answer 36

excess glucose is used to make fat

Question 37

Describe the biochemical basis of diabetic retinopathy. (pg.46)

Answer 37

Excess glucose in the blood is converted into glucitol (s​orbitol​) via a
non­specific dehydrogenase.​Sorbitol is highly osmotic, and it creates osmotic
imbalances in various tissues such as the CVS, kidney (causes nephropathy),
and retina (causes diabetic retinopathy)​.***

Question 38

What is glycation​?

Answer 38

non­enzymatic protein glycosyl transfer***
○ the amino­terminal of proteins is glycated with glucose at the reactive aldehyde
group to form glycoconjugates. This process is called glycation (non­enzymatic).
These glycan conjugates are very deleterious b/c it causes various metabolic
defects, leading to diabetic retinopathy, neuropathy, hemoglobin A1c formation,

Question 39

Explain the biochemical basis of hypoglycemia.

Answer 39

Hypoglycemia can be caused by a pancreatic tumor, which results in the
overproduction of insulin.
○ High insulin activity will lead to increased uptake of glucose from blood into cells,
thereby decreasing blood glucose levels.

Question 40

What are GLUT’s?

Answer 40

GLUTs​­ tissue specific glucose transporter that transport glucose from blood into
cells, the receptors of insulin. GLUcose Transporters.

Question 41

What is the normal fasting level of glucose in blood (explain it in percent and mM
concentrations).

Answer 41

~80- ­120mg/dl, or
○ ~4.5- ­7mMoles/L
○ 4­-6%

Question 42

Muscle can respond to insulin, however it doesn’t respond to glucagon.

Answer 42

muscles dont have glucagon receptors

Question 43

Why are proteins more prone to non­enzymatic glycation?

Answer 43

Proteins have terminal amino residues and reactive lysines.