Lesson 13 - Pyruvate Dehydrogenase Complex (PDC) and the Citric Cycle (TCA) Flashcards

1
Q

is a central area of metabolism

A

a process where anabolic and catabolic pathways intersect

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2
Q

TCA:

A

intersection of amino acid, fatty acid and carbohydrate metabolism

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3
Q

considering the structure of pyruvate (C3H3COO3-), how does pyruvate get into the mitochondrion

A

a mitochondrial pyruvate carrier

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4
Q

how does the structure of the mitochondrion facilitate the exchange of metabolites betwween the TCA and ETC

A

IM is embedded with components of the ETC
– reduced coenzymes are “fed” directly in

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5
Q

predict what the most importnat produts are that are directly produced from glycolysis and the citric acid cycle

A

e-‘s in the form of reduced coenzymes

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6
Q

how does the cell harness (conserve) potential energy through these processes to synthesis ATP during oxidative phosphorilation

A
  • the free energy of electron transfer from NADH –> H2O is conserved in a H+ gradient across the IM
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7
Q

pyruvate dehydrogenase complex, PDC, an example of a multienzyme complex:

A

1 - two or more noncovalently associated enxymes
2 - catalyze sequential reactions
3 - increase the frequency of collisions and overall reaction rate (free enzymes very close together)
4 - place a series of reactions rate coordinate control (allosteric molecule)

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8
Q

requires 5 cofactors (mostly from diet)

A

1 - coenzyme A (CoA or CoA-SH)
2 - Lipoamide
3 - TPP
4 - NAD+
5 - FAD

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9
Q

where does NAD come from

A

dietary Niacin (vitamin B3)
- sever niacin deficiency causes the disease pellagra
symptopms include skin rahs, diarrhea, and neurological problems
vitamin b missing in a corn rich diet
^^^ present in corn, but in the form of a protein bound form (NAD+/NADH) that drastically reduces its absorption in the intestine
- soaking corn in lime solution (calcium oxide) releases niacin from it’s protein-bound form

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10
Q

where does FAD come from

A
  • dietary riboflavin
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11
Q

where does CoA come from

A
  • derived from dietary pantothenic acid
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12
Q

where does TPP come from

A

dietary thiamine
- polished rice is deficient in thiamine
- whole rice is rich in thiamine

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13
Q

dietary lipoic acid is covalently attached to

A
  • a Lys residue on E2 –> involved in a group transfer reaction
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14
Q

Reaction 1: to get the acetyl-CoA

A

pyruvate + NAD+ + CoA –> acetyl-CoA + NADH + CO2

by pyruvate dehydrogenase complex (E1 + E2 + E3)

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15
Q

what kind of molecule is Acetyl-CoA

A

thioester; “high energy” –> FAR from equilibrium

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16
Q

what type of reaction is reaction 1

A

group transfer
- pyruvate reacts with the TPP carbination of E1 to form an addition product that undergoes decarboxylation giving hydroxyethyl-TPP

17
Q

what type of reaction is rxn 2

A

group transfer
- the hydroxyethyl group is transferred by E1 to a lipoamide swinging arm on E2 resulting in oxidation of the 2-carbon fragment to an acetyl group and reduction of the lipoamide disulfide to dihydrolipoamide (with actyl group bound)

18
Q

for reaction 3 does the lipoamide emerge from this reaction fully oxidixed or reduced

A

fully reduced

19
Q

does NAD+ emerge from rxn 4&5 in the oxidized or reduced state

A

reduced?

20
Q

rxn 1

A

acetyl-CoA + oxaloacetate + H2O –> CoA + Citrate

by citrate synthase
- irreversible under cellular conditions, delta G negative

21
Q

rxn 2

A

citrate <–> isocitrate

by aconitase

22
Q

rxn 3

A

isocitrate + NAD+ –> alpha ketoglutarate + NADH + CO2 + H+

by isocitrate dehydrogenase

– oxidative decarboxylation, NADH + H+ generated

23
Q

rxn 4

A

alpha ketoglutarate + CoA + NAD+ –> Succinyl - CoA + NADH + CO2 + H+

by alpha ketoglutarate dehydrogenase

– mechanistically identical to PDC

24
Q

rxn 5

A

succinyl - CoA + GDP + Pi <–> succinate + GTP + CoA

by succinyl-CoA synthetase

– energy of thioester bond hydrolysis
- conserved in substrate level phosphrylation

25
Q

rxn 6

A

succinate + FAD <–> Furmarate + FADH2

by succinate dehydrogenase

– AKA complex II of the ETC
– located in IM NOT MATRIC; FADH2 produced

26
Q

rxn 7

A

fumarate + H2O <–> malate

fumarase

– stepwise addition of H2O across double bond

27
Q

rxn 8

A

malate + NAD+ <–> Oxaloacetate + NADH + H+

28
Q

what reactions are the far equilibrium rxns

A

1,3,4

29
Q

TCA net equation

A

acetyle-CoA + 3 NAD + FAD + GDP + P + 2H2O –> CoA-SH + 3NADH + FADH2 + 3H+ + GTP + 2CO2

30
Q

reduced coenzymes funneled into ETC …

A

ultimately produce significant ATP

31
Q

+ NAD+, CoA, ADP, Ca 2+ indicates

A

that the cell needs to make ATP, low energy charge (EC); catabolize glucose to synthesize ATP

32
Q

what are the targets of regulation in PDC and TCA

A

far from equilibrium rxns

33
Q
  • NADH, ATP indicate
A

cellls have an ample ATP, high energy charge (EC); store glucose, don’t catabolize