TCA Cycle Flashcards by Rebecca Ruthberg

TCA cycle produces

1 GTP
3NADH/1FADH2
2Co2

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pyruvate - what corresponding a.a.

alanine

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what is a.a. for oxaloacetate

aspartate

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pyruvate is precurser to what a.a

alanine

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αketoglutarate is precurser to what a.a

glutamate

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what is start ot TCA

pyruvate

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pyruvate only produced by

glucose

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pyruvate dehydrogenase converts pyruvate to

acetyla CoA

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for pyruvate to get into mitochondria needs what transporter

secondary active transport

uses the gradient of hydrogen to transport pyruvate against concentration grdient

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pyruvate dehydrogenase complex of many genes coming together for form complex molecule with what three activities

pyruvate dehyrogenase
dihydrolipoyl transacetylase
dihydrolipoyl dehydrogenase

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in TCA pyruvate acts as a

co-enzyme

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write out the steps of pyruvate dehyrogenase complex

pg 6

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what are products of pyruvate dehyrogenase complex

NADH + H+

CO2

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PDC stands for

pyruvate dehydrogenase complex

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PDH kinase inactivates

pyruvate dehydrogenase complex

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pyruvate dehydrogenase complex inhibited by

acetyl CoA, NADH

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pyruvate dehydrogenase complex activated by

CoA, NAD+

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PDH phosphatase activates

pyruvate dehydrogenase complex

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affect mitochondria in any way you have

lactic acidosis

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PDH deficiency what are consequences

progressive psychomotor retardation often with damage to brainstem & basal ganglia.
Brain dependent on glycolysis for energy & sensitive to acidosis.

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brain is sensitive to

acidosis and low glucose

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common mutation for PDH defiicency is located where

X-linked

when girls haveit symptoms not as bad - boys have it more severly

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PDH deficiency is a type of subacute necrotizing encephalomyelopathy called

Leigh Syndrome/disease

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pyruate carboxylase, pyruate to

pyruvate to oxaloacetate

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intermediates of TCA cycle called what kind of reaction

anapleoritc

any reactions that produce intermeciate of TCA cycle called

anapleoritc rxn

arsenate

acts on glycolysis by competing with Pi

acetyl-CoA unique bc it can come from

a.a fatty acid glucose

if you eat extra carbohydrates you will produce fat b/c of

acetyl-CoA

list sequence of events in the citric acid cycle

pg 14

coenzyme A

nucleotide with purine, ribose, phosphoester, etc. it is a nucleotide . coenzyme A is attached to acetyl to form acetyl-CoA

hyrolysis of thioesters is strongly

favorable

what is an important donor of acyl groups

acetyl co-a

what is formed by condensation of acetyl-CoA and oxaloacetate

C-C bond

why is acetyl CoA ready to go more than glucose

the thioester is ready to go - it is a high energy bond. it comes from fat, carbs, a.a

acetyl CoA + oxaloacetate + citrate synthase is reversible or irreversible

irreversible step

draw out the allosteric regulation os isocitrate dehydrogenase

pg 20 - draw mech on right

what inhibits isocitrate dehydrogenase

ATP | NADH

if inihbit isocitrate dehydrogenase what accumulates

citrate

how does NADH affect rate of isocitrate dehydrogenase

affects the allosteric activation

α ketoglutarate is

ketoacid

ketoacid is precurser for

a.a. → glutamate

pyruvate is a

ketoacid

pyruvate dehyrogenase uses same tools as

α ketoglutarate dehydrogenase complex

how does arsenite poisioning affect α ketoglutarate dehydrogenase complex

disables lipoic acid

α ketoglutarate dehydrogenase has same mechanism as

pyruvate dehyrogenase complex | oxidation of isoleucine(pg 22)

write out steps of TCA

biochem book | make diagram & look through his slides and add important steps

succinate dehydrogenase contains covalently bound

FAD

succinate dehydrogenase is found where

inner mitochondrial membrane

fumarate is hydrated to malate by

fumarase

besides TCA where is fumarate produced

urea cycle purine synthesis catabolism of Phe, Tyr

malate is one of the few molecules that can

go in and out of mitochondria

malate to oxaloacetate -describe its favorability

unfavorable, it wants to stay as malate

how does cell move malate to oxaloacetate

the concentration of oxaloacetate is very small to help pull rxn forward

concentration of oxaloacetate in cell is

very low, it helps pull the reaction forward

what are the inhibitors of citric acid cycle

NADH & ATP

what are the activators of citric acid cycle

NAD+ and AMP

fatty acids produce a lot of

acetyl-CoA

if a lot of acetyl-Coa is produced (fatty acid) what happens to affinity of enzyme

it goes down, you don't need pyruvate to be converted to acetyl-CoA when you already have a lot of acetyl-CoA coming from fatty acids

acetyla CoA processing by TCA cycle produces how much ATP

10 mol

NADH = how many ATP

2.5

FADH2= how many ATP

1.5

TCA intermediates are

amphibolic and exergonic

TCA intermediates are amphibolic - intermediates from TCA can be used

for things besides energy, the intermediates can go off and do synthesis of something else

if pulling a lot of intermediates out of TCA cycle what happens to speed/direction of TCA

it will slow down, need to replenish the intermediates

anaplerotic reactions

substrate and produce intermediates of TCA cycle

pyruvate carboxylase uses pyruvate, HCO3-, ATP to produce

oxalocetate + ADP + P

PEP carboxykinase produces

oxalocetate

how does arsenate act on glycolysis

competes with Pi

how does arsenite act on TCA

disables PDC

besides pyruvate, how is Acetyl CoA made

fatty acids | amino acids

how does Acetyl-CoA donate acyl groups

feeding two-carbon units into metabolic pathways | synthesis of fatty acids

in TCA cycle what is the only reaction with C-C bond formation

the first one - acetyl-Coa + oxaloacetate → citrate

during the first rxn in TCA oxaloacetate acts as a

electrophile

fluoroacetate inhibits

aconitase (step 2)

draw out TCA cycle

yay

where is the first oxidation of TCA

step# 3 with isocitrate dehydrogenase

what activates isocitrate dehydrogenase

ADP | Ca2+

what inhibits isocitrate dehydrogenase

ATP | NADH

how do isocitrate, NAD+ and NADH bind to isocitrate dehyrogenase

active site

how do ADP and Ca2+ bind to isocitrate dehydrogenase

bind separate allosteric sites

what does ADP do to isocitrate dehydrogenase

ADP induces all subunits to be in their active conformation & reduces Km

what does NADH do to isocitrate dehydrogenase

NADH (a product of the reaction) reduces the rate by affecting the allosteric activation

what does ADP do to Km when it binds to isocitrate dehydrogenase

reduces Km aka it makes the enzyme work better by affecting the allosteric activation

where is second oxidation in TCA

step#4 | α-ketoglutarate →succinyl-CoA

what are cofactors in step# 4 α-ketoglutarate →succinyl-CoA

thiamine pyrophosphate, lipoic acid, FAD, NAD+, CoA as co-factors

what inhibits α-ketoglutarate dehydrogenase complex

NADH & succinyl CoA

what activates α-ketoglutarate dehydrogenase complex

Ca2+