Glycogen Metabolism Flashcards

1
Q

glycogen contains which 2 kinds of bonds?

A

(a-1,4) linkages and (a-1,6) linkages

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2
Q

which end does glycogen degradation and synthesis occur?

A

non reducing ends

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3
Q

what does glycogen phosphorylase do?

A

cleaves (a-1,4) linkages until it reaches the 4th from the branch point
(directly phosphorylates the glucose to make G1P)

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4
Q

what does debranching enzyme transferase do?

A

transfers a block of 3 units to the nonreducing end of the chain

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5
Q

what does debranching enzyme (a-1,6) glucosidase do?

A

cleaves the last remaining (a-1,6) linked glucose

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6
Q

what does phosphoglucomutase do?

A

interconverts between glucose-1-P (G1P) and glucose-6-P (G6P)

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7
Q

what is PLP (pyridoxal-5-phosphate)?

A

a derivate of vitamin B6 and cofactor for glycogen phosphorylase

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8
Q

what is the mechanism of PLP?

A

the phosphate of PLP is involved in acid/base catalysis and covalently binds to a lysine residue in glycogen phosphorylase

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9
Q

what is 1,5-gluconolactone?

A

competitive inhibitor of glycogen phosphorylase (mimics its structure)

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10
Q

what helps phosphoglucomutase interconvert between G1P and G6P?

A

a phosphorylated serine helps in phosphate exchange

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11
Q

what are the 3 key steps of glycogenesis?

A
  1. activation of glucose
  2. formation of an a-1,4 bond
  3. formation of an a-1,6 bond
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12
Q

what is the UDP-glucose-pyrophosphorylase equation?

A

G1P + UTP = UDP-glucose + PPi

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13
Q

where does G1P come from?

A

phosphoglucomutase

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14
Q

what other modifications are used to “activate” metabolites?

A
  • acetyl CoA ~ acetate

- ATP ~ Pi

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15
Q

what is the glycogen synthase equation?

A

UDP-glucose + glycogen(n) —> glycogen(n+1) + UDP

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16
Q

what does glycogen synthase do?

A
  • makes linear glucose chains
  • forms a-1,4 glyosidic bonds at non-reducing ends
  • resulting in linear enlargement of an existing glycogen molecule
17
Q

what is glycogenin?

A
  • primer for glycogen synthase
  • autocatalytic tyrosine glycosyl transferase
  • the enzyme is the substrate
18
Q

what does branching enzyme do?

A
  • cleaves a a-1,4 bond to yield a 7-unit chain

- forms an a-1,6 bond between 7-unit chain and another glycosyl unit

19
Q

what does glycogenesis require and how much?

A
  • energy

- enzymatically rephosphorylating UDP costs an ATP (1 G6P in glycogen = 1 ATP)

20
Q

fasting stimulates which type of pathways?

A

glucagon stimulates catabolic pathways, and often inhibits anabolic pathways

21
Q

eating stimulates which type of pathways?

A

insulin drives glucose into cells and stimulates anabolic pathways, and often inhibits catabolic pathways

22
Q

what are the steps to breakdown glycogen?

A
  • glucagon activates a GPCR
  • that stimulates adenylate cyclase to make cAMP
  • that activates PKA (protein kinase A)
  • results in a phosphorylation cascade ultimately phosphorylating and activating glycogen phosphorylase
23
Q

how is glycogen synthesized?

A

high glucose/insulin promotes…

  • dephosphorylation and activation via PP1
  • allosteric activation by upregulating G6P
24
Q

what inhibits glycogen synthase?

A

PKA

25
Q

true or false: phosphoglucomutase is unidirectional

A

false, it is bidirectional and sensitive to G6P levels

26
Q

what causes upregulation of G6P and which process does it lead to?

A

fed state leads to upregulation of G6P causing glycogenesis

27
Q

what causes downregulation of G6P and which process does it lead to?

A

fasted state leads to downregulation of G6P causing glycogenolysis

28
Q

what is the last step of glycogenolysis?

A

phosphoglucomutase

29
Q

describe type 1: Von Gierke’s disease

A
  • Glucose-6-phosphotase deficiency

- leads to glycogen accumulation in the liver and kidneys

30
Q

what is the role of glycogen in the liver?

A

dephosphorylation -> glucose -> export

31
Q

what is the role of glycogen in skeletal muscle?

A
  • glycolysis -> pyruvate -> ATP
    OR
  • PPP -> NADPH, R5P
    this is because skeletal muscle is usually recruited during exercise, where we need energy fast