Metabolism 5 Flashcards

1
Q

Describe glycogen.

A

Glycogen, a Highly Branched Storage Form of Glucose, Is Required as a Ready Source of Energy.

Glycogen is composed of
glycosyl residues, mostly linked by alpha-1, 4 glycosidic linkage.

Branches arise from frequently
alpha-1, 6 glycosidic linkage.

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2
Q

How does hepatic glycogen concentration change throughout the day (in regards to meals).

A

Hepatic glycogen concentration increases after meals and declines between meals.

graph p 4

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3
Q

Glycogen is stored in muscle and liver for quite different reasons. Explain.

A

Glycogen is stored in muscle and liver for quite different reasons. Muscle glycogen is a
fuel reserved for the production of ATP within that tissue. Liver glycogen is a glucose reserve for the maintenance of blood glucose concentration.

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4
Q

Describe glycogen in the liver. What enzyme is key to adding glucose 1-P to growing glycogen chains?

(How does blood glucose coming into liver get converted to liver glycogen and back)?

How much glycogen can the liver store? What happens when that capacity is reached?

What is the key enzyme needed to remove glucose moieties from glycogen?

What enzyme is crucial to allowing glucose from liver glycogen to contribute to blood glucose?

A
  1. glycogen synthase is the key enzyme which adds glucose 1-P to growing glycogen chains

(glucose from cytoplasm/blood…to glucose-6-P, then glucose-1-P to liver glycogen… and back to 1-p then 6-P)

  1. the liver can store about 100g of glycogen. Once this amount is stored, excess glucose is redirected toward FA synthesis.
  2. glycogen phosphorylase is the key enzyme involved in removing glucose moieties from glycogen
  3. the liver expresses glucose-6-phosphatase. Thus glucose from liver glycogen can directly contribute to blood glucose levels.

p5

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5
Q

How is muscle glycogen used?

Does it contribute to blood glucose in times of hypoglycemia?

When is muscle glycogen mobilized?

Does muscle glycogen express glucose-6-phosphatase? Explain implications.

How much glycogen can muscle store? What is happens when capacity is reached?

A

Muscle glycogen is not used to increase blood glucose in times of hypoglycemia. Muscle glycogen is mobilized during exercise. Because muscle does not express glucose-6-phosphatase, glucose-6-phosphate cannot leave the cell, instead it it used for ATP production.

Muscle can store about 400g of glycogen. Excessive glucose can be converted to FAs and stored as TGs.

glucose from cytoplasm…glucose-6-P to glucose-1-P then to muscle glycogen..glycogen back to 1-P and 6-P then undergoes glycolysis.

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6
Q

Describe/draw the synthesis and breakdown of hepatic and muscle glycogen.

A

Slide 7, p 6

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7
Q

Describe/draw the synthesis of muscle glycogen and breakdown of muscle glycogen during exercise.

A

p 6

GLUT4 bc muscle

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8
Q

What are the sources of energy during exercise? Which are used up first? Which is most sustainable?

(Draw).

A

ATP and creatine phosphate- used up in minutes

anaerobic glycolysis, muscle glycogen (5 min)

at 3 minutes aerobic oxidation, muscle glycogen, plasma glucose, liver glycogen… starts to drop off at about 3 hours

at 4 min aerobic oxidation/plasma FFA and adipose tissue triglycerides slowly/steadily rises, peaks at 1.5 hours and levels off.

See slide 9, or p 7

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9
Q

Show/draw a branching diagram of glycogen synthesis and degradation.

Describe what enzymes it requires.

A

Slide 10, p 8

Glycogen synthesis requires an enzyme (glycogen synthase) that adds
glucosyl units in an alpha-1,4 linkage. It also requires a branching enzyme.

Glycogen degradation requires an enzyme (glycogen phosphorylase)
that removes glucosyl units from an alpha-1,4 linkage and a
debranching enzyme. The debranching enzyme has two activities: transferase & alpha-1,6-glucosidase.

slide 12, p 9

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10
Q

What is glycogenin? Describe its function.

A

A polypeptide of 332 amino acids called Glycogenin serves as a primer for glycogen synthesis.

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11
Q

Are glucose/glycogen osmotically active?

A

Glucose is osmotically active,

whereas glycogen is not.

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12
Q

Describe the regulation of glycogen phosphorylase activity by multiple second messenger pathways.

Describe the role of AMP, Ca, calmodulin, insulin.

A

p 10, 11

AMP: The b form of muscle glycogen phosphorylase can be allosterically activated by AMP.

Ca2+ can activate phosphorylase kinase via binding to calmodulin, a subunit of this enzyme.

Insulin inhibits glycogen phosphorylase by activating phosphoprotein phosphatase; the latter enzyme dephosphorylates glycogen phosphorylase.

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13
Q

Describe the regulation of glycogen synthase by covalent modification.

A

Phosphorylation converts

glycogen synthase from its active alpha form to its inactive beta form.

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14
Q

Describe role of insulin on glycogen synthase.

A

Insulin activates glycogen synthase by activating phosphoprotein phosphatase; the latter enzyme dephosphorylates glycogen synthase.

Insulin inhibits glycogen phosphorylase by activating phosphoprotein
phosphatase; the latter enzyme dephosphorylates glycogen phosphorylase.

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15
Q

How is the b form of glycogen synthase activated?

A

Glucose 6-phosphate: The b form of glycogen synthase can be allosterically activated
by glucose 6-phosphate.

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16
Q

Describe the overall effects of increased cAMP; the similarities and differences in muscle and liver.

A

p 12

slides 28-29

17
Q

Describe/draw the Phosphoinositide Mechanism
(another “cascade” mechanism)

Ca2+ Mechanism (Muscle)
(Ca2+ activates a Ca2+-dependent PK)

A

p 13

IP3 increases Ca2+
Ca2+ activates a Ca2+-dependent PK
Diacylglycerol (DAG) activates PKC

18
Q

Explain how insulin affects glycogen syntehsis in muscle and liver.

A

Insulin acts via a plasma
membrane receptor to promote
glycogen synthesis in muscle.

Insulin acts via a plasma membrane receptor to promote glycogen synthesis in liver.

p 14

19
Q

Inherited glycogen storage diseases can affect tissue glycogen levels,
fasting blood glucose levels, lipid metabolism and other pathways.

Describe Von Gierke Disease (defective enzyme, affected organ, glycogen, and clinical features).

A

Slide 36
p 15

glucose-6-phosphatase deficient

liver and kidney

increased glycogen, normal structure

Clinical features: enlarged liver, failure to thrive, severe hypoglycemia, hyperuricemia, gouty arthritis, hyperlipidemia, mental retardation, lactic acidosis

20
Q

Glucagon regulates the pathways of glycolysis, gluconeogenesis and
glycogen metabolism in the liver.

How does it affect concentration of blood glucose?

A

Overall Effect: Increase the Concentration of Blood Glucose

21
Q

How does glucagon affect glycolysis?

A

Glucagon Inhibits Glycolysis.
A. Inhibits PFK-2, which leads to decreased fructose-2-6-bisphosphate.
Decreased fructose-2,6-bisphosphate leads to decreased activity of PFK-1.
B. Inhibits pyruvate kinase

22
Q

How does glucagon affect gluconeogensis?

A

Glucagon Activates Gluconeogenesis.

A. Inhibits PFK-2, which leads to decreased fructose-2-6-bisphosphate.
Decreased fructose-2,6-bisphosphate leads to increased activity of
fructose-1,6-bisphosphatase.

B. Inhibits pyruvate kinase; by inhibiting glycolysis, gluconeogenesis is promoted.

23
Q

How does glucagon affect glycogen synthesis?

A

Glucagon Inhibits Glycogen Synthesis.

A. Inhibits glycogen synthase

24
Q

How does glucagon affect glycogenolysis/degradation?

A

Glucagon Activates Glycogenolysis/Degradation.

A. Activates glycogen phosphorylase
B. Activates phosphorylase kinase

25
Q

Describe the purpose of allocating glucose to the Pentose Phosphate Pathway
(Hexose Monophosphate Shunt)

A

slides 40-52 p 17

A Small Portion of Glucose Is Diverted to the Pentose Phosphate Pathway
in Order to Generate NADPH and Ribose 5-Phosphate.

26
Q

Describe the metabolism of glucose by the pentose phosphate pathway. What is produced?

A

The pentose phosphate pathway uses a relatively small portion of glucose. The
metabolism of glucose by this pathway produces the following.

a. NADPH - used in lipid biosynthesis
b. Ribose 5-Phosphate - used in the biosynthesis of DNA, RNA, CoA, ATP, etc.
c. Intermediates that can be further metabolized by glycolysis.

27
Q

Where is the pentose phosphate pathway particularly active?

A

The pathway is particularly active in tissues having active lipid biosynthesis.

28
Q

What is the rate limiting enzyme in pentose phosphate pathway?

What can deficiency of this enzyme lead to?

This disease is found especially in individuals of what heritage?

What does disease result from?

A

The rate limiting enzyme is GLUCOSE 6-PHOSPHATE DEHYDROGENASE.

A deficiency of this enzyme can lead to a drug-induced hemolytic anemia. This disorder is found particularly in individuals with a Mediterranean (GdMed) or Black (GdA-) heritage.

The disease results from an inability of the affected red blood cells to maintain adequate amounts of reduced NADPH; NADPH is normally required to reduce glutathione, which in turn reduces the SH on various proteins.

p 18

29
Q

Show how destruction of H2O2 is dependent on reduction of oxidized
glutathione by NADPH generated by pentose phosphate pathway.

A

p 17

30
Q

What can deficiency of transketolase lead to?

A

A deficiency of transketolase, another enzyme in the pentose phosphate pathway, can lead to Wernicke-Korsakoff Syndrome. The most common cause of Wernicke-Korsakoff
syndrome is thiamine deficiency.