Lecture 22, Glyc Metabolism (Zaidi) Flashcards

1
Q

Describe the structure of glycogen.

A

Long chain homopolymer of glucose molecules with branches

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2
Q

What are the glucose molecules within a chain of glycogen linked together by?

A

alpha-1,4-glycosidic bonds

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3
Q

What kind of bonds are the branch points of glycogen formed by?

A

alpha-1,6-glycosidic

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4
Q

What are the 2 kinds of ends of a glycogen molecule?

A

Non-reducing and reducing

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5
Q

Describe the non-reducing end of a molecule of glycogen.

A

Contain a terminal glucose with a free hydroxyl group at C4

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6
Q

Describe the reducing end of a molecule of glycogen.

A

Consists of a glucose monomer connected to glycogenin

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7
Q

Why is glycogenin important?

A

Creates a short glycogen polymer on itself and serves as a primer for glycogen synthesis

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8
Q

From which end is glycogen degraded and extended?

A

Non-reducing end

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9
Q

Where is glycogen stored?

A

Liver, muscle, and other tissues

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10
Q

How is glycogen stored?

A

As granules, but the granules also contain enzymes needed for glycogen metabolism

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11
Q

T or F: Defects in the enzymes contained in the glycogen granules can lead to disorders.

A

True.

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12
Q

What is the function of liver glycogen?

A

Regulates blood glucose levels

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13
Q

What is the function of muscle glycogen?

A

Provides reservoir of fuel (glucose) for physical activity

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14
Q

What is an overview of glycogen metabolism?

A

Regulated storage and release of glucose

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15
Q

T or F: The synthesis and degradation of glycogen involve different pathways, but are regulated by the same mechanism.

A

False. The synthesis and degradation of glycogen involve different pathways and are regulated independently.

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16
Q

How is glycogen metabolism regulated?

A

Allosteric control, covalent modification through reversible phosphorylation of key enzymes, hormonal control

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17
Q

There are 3 key steps in glycogenesis. What is the purpose of the first step?

A

Trapping and activation of glucose

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18
Q

In glycogenesis, what traps glucose in the hepatocytes and muscle cells?

A

Glucokinase/hexokinase catalyze phosphorylation of glucose to glucose 6-phosphate

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19
Q

What enzyme reversibly isomerizes glucose 6-phosphate to glucose 1-phosphate?

A

Phosphoglucomutase

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20
Q

What is the role of uridine diphosphate (UDP) glucose pyrophosphorylase? What is generated?

A

Transfers the glucose 1-phosphate to UTP; UDP-glucose is generated

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21
Q

How does UDP glucose pyrophosphorylase generate energy?

A

Breakdown of pyrophosphate to Pi generates energy

22
Q

What is the formation of UDP glucose catalyzed by?

A

UDP-glucose pyrophosphorylase

23
Q

There are 3 key steps in glycogenesis. What is the purpose of the second step?

A

Elongation of a glycogen primer

24
Q

What is the rate-limiting enzyme of glycogenesis?

A

Glycogen synthase

25
Q

What is the enzyme that adds glucose to the preexisting glycogen polymer?

A

Glycogen synthase

26
Q

The peexisting glycogen polymer serves as a ___ to which glucose units are added in the elongation of glycogen.

A

Primer

27
Q

What is the mechanism of glycogen synthase? What kind of bond is formed?

A

Catalyzes transfer of glucose from UDP-glucose to non-reducing end of glycogen chain; Forms alpha-1,4-glycosidic bond between glucose molecules

28
Q

There are 3 key steps in glycogenesis. What is the purpose of the third step?

A

Branching of glycogen chains

29
Q

When a glycogen chain reaches about 11 residues long, what happens?

A

A fragment of the chain (about 7 residues) is broken off at an alpha-1,4-link and reattached elsewhere through an alpha-1,6- link

30
Q

What is the enzyme that allows the branching of glycogen?

A

Glucosyl (4:6) transferase

31
Q

How far away must a new branch point be from a preexisting branch point?

A

At least 4 residues away

32
Q

Why is the branching of glycogen molecules important?

A

Branching increases solubility of glycogen and increases number of terminal non-reducing ends; Increases rate at which glycogen can be synthesized and degraded

33
Q

What does the breakdown of glycogen release?

A

Glucose 1-phosphate

34
Q

What is broken down glycogen (glucose 1-phosphate) called?

A

Glycogen remnant (n-1)

35
Q

After glycogen breakdown, what is remodeled to permit further degradation?

A

Glycogen remnant

36
Q

What is glucose 1-phosphate converted to? Where can this be used?

A

Glucose 6-phosphate; Glycolysis, free glucose for release into blood stream, PPP (NADPH and ribose derivative)

37
Q

In glycogenolysis, what are the roles of the 4 key enzymes?

A
  1. Degrade glycogen (chain shortening)
    2 and 3. Remodel glycogen remnants
  2. Convert glycogen breakdown product suitable for further metabolism
38
Q

What catalyzes the cleavage of glycogen?

A

Glycogen phosphorylase (GP)

39
Q

What is the rate-limiting enzyme of glycogenolysis?

A

Glycogen phosphorylase (GP)

40
Q

Where does chain shortening occur in glycogenolysis?

A

Non-reducing end of polymer

41
Q

What is the mechanism of GP?

A

Adds orthophosphate and releases glucose residue as G1P; Uses pyridoxal phosphate (vitamin B6) as a cofactor

42
Q

How long does the phosphorolysis of glucose residues continue?

A

Until the GP gets within 4 residues of the alpha-1,6-linkage of a branch point

43
Q

What is the role of phosphoglucomutase?

A

Converts G1P to G6P

44
Q

What is the mechanism of phosphoglucomutase?

A

Phosphoryl group is transferred form enzyme to the substrate, and a different phosphoryl group is transferred back to restore the enzyme to its initial state

45
Q

What is the role of transferase in glycogenolysis?

A

Transfers a block of 3 of the remaining 4 glucose to the non-reducing end of the main chain forming an alpha-1,4 bond

46
Q

What is the role of the debranching enzyme (alpha 1,6 glucosidase)?

A

Cleaves alpha-1,6 bond of single remaining glucose residue to release the free glucose

47
Q

In glycogenolysis, what is glucose phosphorylated by?

A

Hexokinase

48
Q

What enzymes convert branched glycogen into a linear structure for further action by GP?

A

alpha-1,6-glucosidase and transferase

49
Q

T or F: G6P cannot get out of the cell.

A

True.

50
Q

Which is the only organ that has glucose 6 phosphatase?

A

Liver

51
Q

What does the liver do with glucose 6 phosphatase?

A

Converts G6P to glucose, which can be released in the bloodstream