METABOLISM SYLLABUS 3: Fates of Pyruvate Flashcards

1
Q

what can happen to pryuvate from glycolysis?

A

1) reduced to LACTATE via LDH in RBC, exercising muscle, embryonic tissue = ANAEROBIC GLYCOLYSIS
2) enter MITO for further metabolism by PDH to ACETYL CoA = AEROBIC GLYCOLYSIS

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2
Q

what does LDH reaction catalyze

A

reduces PYRUVATE to LACTATE

this is REVERSIBLE

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3
Q

why is LDH reaction important in RBC?

A

critical to RBC here b/c NADH reodixidzed back to NAD+, which is needed for glycolysis to continue at the G3PDH step

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4
Q

what do tissues w/ mito do with the LDH reaction?

A

oxidize the NAD+ from the LDH reaction to NADH after it is transported into the mito by the respiratory chain

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5
Q

how is LDH reaction improtant in muscle contraction?

A

reoxidizes NADH whenever glycolysis is very rapid - so when muscle contraction, high insulin levels, tumor cells

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6
Q

what is ANAEROBIC glucolysis?

A

glycolysis without oxygen

when lactate is the final product of glycolysis, and net of glycolysis is :

glucose + 2ADP + Pi -> 2 Lactic Acid + 2 ATP

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7
Q

what happens to lactate produced from LDH?

A

1) high levels of lactic acid leaves the RBC/muscle/tissue where it was produced, -> blood

high levels of lactate in blood alter blood pH, cause cramps, aggravate gout

2) other lactate enters tissues -> reoxidized back to pyruvate -> undergoes PDH reaction for energy production or can be converted to glucose in liver during gluconeogenesis

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8
Q

how does the RBC or brain or heart know which direction to go w/ the LDH reaction?

A

this question is b/c the LDH reaction is reversible

LDH is a **tetramer **made of 2H and 2M subunits;

therefore have 5 different is**ozymes/isoforms, **

H4, H3M, H2M2, HM3, M4

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9
Q

where are the H vs. M isoforms of LDH found?

what are their properties?

A

H isoforms: brain, heart; have higher affinity for lactate and NAD; inhibited by high levels of pyruvate

M isoforms: RBC, skeletal muscle; have lower affinity for lactate and NAD; not inhibited by high levels of pyruvate

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10
Q

what happens to pyruvate in yeast cells?

A

it is converted to ethanol (alcohol) by **pyrvuate decarboxylase **

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11
Q

describe the pyruvate decarboxylase reaction

A

how pryvuate -> alcohol in yeast cells

pyruvate + TPP -> CO2 + acedylaldehyde, by pyruvate decarboxylase

acetylaldehyde + NADH -> ethanol + NAD, by alcohol DH

NET: glucose -> 2 ethanol + 2CO2 + 2ATP

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12
Q

what are mammals lacking re: alcohol fermentation rxn?

A

mammals do not have yeast pyruvate decarboxylase

thus mammals oxidize ethanol back to acetylaldehyde by alcohol DH, but that becomes acetyl CoA

otherwise, if we had pyruvate decarboxylase, glucose -> ethanol, as yeast do

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13
Q

what happens to pyruvate in most tissues?

A

undergoes the PDH reaction, converting it to acetyl COA

acetyl CoA can be further oxidized in the TCA cycle, generating NADH and FADH2 for energy production by the respiratory chain

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14
Q

what is the naure of the PDH rxn?

A

IRREVERSIBLE

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15
Q

where does PDH reaction occur?

A

mito matrix

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16
Q

what is the net of the PDH reaction?

A

pryuvate + CoASH + NAD -> acetyl CoA + CO2 + NAHD + H

17
Q

what does CoASH do?

A

carries acyl groups like acetyl and fatty acyl groups

contains B vitamin phosphopantethiene and an SH group at its terminus by which acyl groups attach

18
Q

what are the enzymes of the PDH complex?

vitamin cofactors?

A

enzymes: E1, E2, E3, PDH kinase, phosphatase

vitamin cofactors: TPP for E1, lipoic acid for E2, riboflavin for E3, phosphopantetheine for CoASH, niacin for NAD+

19
Q

describe the PDH mechanism

A

1) E1 decarboxylates pyruvate and replaces the CO2 w/ TPP
2) E2 replaces the TPP group w/ lipoamide. Then CoA is added to the reduced lipoamide
3) E3 reduces FAD, regenerating the lipoamide so that E2 is functional again - this matters so that acetyl CoA can keep being produced

20
Q

what inhibits each step of the PDH mechanism? (metabolites)

A

ATP inhibits E1

Acetyl CoA inhibits E2

NADH inhibits E3

aka each of the reaction’s products inhibits that reaction, and these are all signs of high energy

21
Q

what hormonally controls the PDH reaction?

A

PDH Kinase: INHIBITS E1 by phosphorylating it; not effected by glucagon or epinephrine

INSULIN stimulates/increases PDH phosphatase: activates E1

22
Q

what is unique about what happens in the E3 reaction of PDH?

A

reoxidation of FADH2 by NADH is the only case in metabolism in which FADH2 reduces HAD+ to NADH; usually, NADH reduces FAD to FADH2

23
Q

what happens to C3, 4 of the original glucose?

A

comes off as CO2 in the PDH reaction

24
Q

what happens to C1, 6 of the original glucose from glycolysis?

A

form the CH3 of acetyl CoA in PDH

25
Q

what happens to carbons 2, 5 of the original glucose?

A

form the C=O of the acetyl group of PDH reaction

come off as CO2 in the TCA cycle

26
Q

is PDH kinase sensitive to glucagon, epi?

A

no