glycogen and pentose phosphate pathway Flashcards

1
Q

fates of glucose

A

glycolysis, glyogen synthesis/storage or pentose phosphate pathway to generate NADPH and ribose sugars. The later 2 are active when glucose is present in excess of what is needed for glycolysis

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2
Q

Describe the structure of glycogen and why this is important

A

highly branched polymer of glucose monomers. Found primarily in liver and muscle

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3
Q

what controls glycogen breakdown

A

insulin and glucagon

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4
Q

major sites of glycogen storage

A

liver and skeletal muscle- glycogen in muscle must be released as lactate and synthesized into glucose by liver (cori cycle) b/c muscle lacks glucose-6-phosphatase

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5
Q

what is the building block of glycogen and how is it synthesized

A

uridine diphosphate (UDP)-glucose - glucose-6-phosphate > glucose-1-phosphate > UDP-glucose.

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6
Q

glycogen synthase function

A

transfers UDP-glucose to growing glycogen chain- UDP-glucose is transferred to hydroxyl group of glycogen to form alpha 1,4 glycosidic linkage. UDP is displaced and released. Only adds glucose residues if polysaccharide chain haas more than 4 glucose residues.

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7
Q

What forms he initiating site for glycogen synthesis

A

glycogenin

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8
Q

glycogen branching enzyme function

A

After glycogen synthase has added 11 glucose residues, branching enzyme transfers 6 or 7 glucose residues from a chain to an internal site to form α-1,6-linkages that produces a branch point in the growing polymer of glucose molecules. The new branch point must be at least 4 residues away from a pre-existing branch point

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9
Q

Result of abnormal glycogen branching

A

glycogen breakdown is slower which can result in hypoglycemia during fasting or reduced exercise tolerance.

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10
Q

steps in glycogen degradation

A
  1. release of glucose-1-phosphate from glycogen. 2. remodeling of the remaining glycogen to permit further degradation. 3. conversion of glucose-1-phosphate into glucose-6-phosphate for further metabolism or export from the cell.
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11
Q

glycogen phosphorylase function

A

catalyzes the cleavage of glycogen to glucose 1-phosphate. Key regulated enzyme in glycogenolysis. Stops when it reaches 4 residues away from alpha-1,6-glycosidic bond branch point

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12
Q

debranching enzyme function

A

shifts a block of 3 glycosyl residues from one outer branch to the other, converting the branched structure into linear structure so that glycogen phosphorylase can continue

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13
Q

Function of glucagon or epinephrine in glycogen synthesis/breakdown

A

glucagon or epi activate protein kinase A > phosphorylates phosphorylase kinase b converting it to phosphorylase kinase a (active) > this phosphorylates glycogen phosphorylase b (inactive) to the a form (active) > glycogen phosphorylase a begins glycogen breakdown

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14
Q

function of insulin in glycogen regulation

A

insulin causes de-phosphorylation of glycogen phosphorylase (via phosphoprotein phosphatase 1, PP1) and of phosphorylase kinase (via protein phosphatase), ultimately causing glycogen synthesis

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15
Q

liver and skeletal muscles role in glycogen synthesis and degradation

A

In muscle, glycolysis and the TCA cycle/electron transport supplies ATP, and the rate of these pathways increase as the muscle works harder. The liver’s role is to maintain a constant level of glucose by producing glucose when other tissues demand it, and storing it when it is provided in excess by the diet.

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16
Q

regulation of glycogen in fed state

A

glycogen synthase is allosterically activated by glucose-6-phosphate when it is present at elevated concentrations following a meal. In contrast, glycogen phosphorylase is allosterically inhibited by glucose-6-phosphate as well as by ATP. In liver, glucose-6-P serves as the key allosteric inhibitor of glycogen phosphorylase.

17
Q

regulation of glycogen in muscle via calcium

A

During muscle contraction, membrane depolarization promotes calcium release. Calcium binds to calmodulin and the complex activates a phosphorylase kinase which phosphorylates glycogen phosphorylase, activating it, leading to glycogen degradation.

18
Q

regulation of glycogen in muscle via AMP

A

AMP binds to the inactive glycogen phosphorylase and allosterically activates it without the need for phosphorylation. This leads to greater glucose release from glycogen during vigorous exercise where AMP levels rise.

19
Q

regulation of glycogen synthase

A

2 forms: The active form, a, is in the de-phospho form. Glycogen synthase a is converted to b (inactive) by phosphorylation, and the level of inactivation is proportional to the number of phosphate groups attached. The de-phospho form can be activated by allosteric activator, glucose-6-phosphate

20
Q

In liver, which enzyme catalyzes dephosphorylation of glycogen synthase

A

protein phosphatase 1

21
Q

How does glucose-6-phosphate activate glycogen synthase b

A

binds to allosteric site and makes the enzyme a better substrate for dephosphorylatin by PP1

22
Q

hormonal regulation of glycogen synthase

A

Epi and glucagon: activate protein kinase A which phsophorylates and inactivates glycogen synthase. Insulin: activates PP1 and inactivates GSK3, which stimulates glycogen synthesis

23
Q

glucagon regulation of glycogen in liver

A

low blood glucose > glucagon release > activates glycogen phosphorylase kinase in liver > converts glycogen phosphorylase b (inactive) to a (active) >release of glucose into blood. When blood glucose returns to normal > glucose enters hepatocytes > glucose binds allosteric site on glycogen phosphorylase > conformational change > phosphatase removes phosphate from phosphorylase a converting to to inactive glycogen phosphorylase b

24
Q

Functions of pentose phosphate pathway

A

produces NADPH for synthsis of fatty acids and steroids (especially in mammary gland, adrenal cortex, etc), produces ribose-5-phosphate for nucleotide synthesis and glycolytic intermediates.

25
Q

Location of enzymes in pentose phosphate pathway

A

cytosol

26
Q

phases of pentose phosphate pathway

A

oxidative - NADPH generating. Non-oxidative- ribose-5-phosphate and glycolytic intermediate generating.

27
Q

Key steps of pentose phosphate pathway

A

glucose-6-phosphate dehydrogenase catalyzes the first rxn (key committed, and rate limiting) which generates first NADPH.

28
Q

glucose-6-phosphate dehydrogenase deficiency

A

Patients are unable to regenerate GSH, to guard against reactive oxygen species (ROS) and critical sulfhydril groups in hemoglobin become oxidized, forming cross-links and aggregates on the red blood cell membrane called Heinz bodies. These aggregates make the RBC membrane rigid leading to RBC destruction and hemolytic anemia, particularly with exposure to sulfa drugs, fava beans