TCA enzymes.ppsx

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Citric Acid Cycle


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Gylcolysis

TCA Cycle

Electron Transport andOxidative phosphorylation


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The TCA Cycle(aka Citric Acid Cycle, Krebs Cycle)

Pyruvate (actually acetate) from

glycolysis is degraded to CO2 Some ATP is produced

More NADH is made

NADH goes on to make more ATP inelectron transport and oxidativephosphorylation


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Entry into the TCA Cycle Pyruvate is translocated from the cytosol to the

mitochondria

Pyruvate is oxidatively decarboxylated to formacetyl-CoA

Pyruvate dehydrogenase uses TPP, CoASH, lipoicacid, FAD and NAD+

Acetyl-CoA then enters TCA cycle thru citratesynthase


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Pyruvate Dehydrogenase

ComplexComposed of three enzymes:

pyruvate dehydrogenase (E1) (cofactor =

TPP) Dihydrolipoamide acetyltransferase (E2)

(cofactor = Lipoamide, CoA)

Dihydrolipoamide dehydrogenase (E3)(cofactor = FAD, NAD+)


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Pyruvate Dehydrogenase


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Citrate Synthase Only step in TCA cycle that involves the

formation of a C-C bond


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Aconitase Isomerization of Citrate to Isocitrate

Citrate is a poor substrate for oxidation

So aconitase isomerizes citrate to yieldisocitrate which has a secondary-OH, whichcan be oxidized

Aconitase uses an iron-sulfur cluster to positioncitrate (binds OH and carboxyl of centralcarbon)


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Isocitrate Dehydrogenase Oxidative decarboxylation of isocitrate to yield

-ketoglutarate Classic NAD+ chemistry (hydride removal)

followed by a decarboxylation

Isocitrate dehydrogenase is a link to the

electron transport pathway because it makesNADH

Rxn is metabolically irreversible


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-Ketoglutarate Dehydrogenase A second oxidative decarboxylation

This enzyme is nearly identical to pyruvatedehydrogenase - structurally andmechanistically

Five coenzymes used - TPP, CoASH, Lipoic acid,NAD+, FAD


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Succinyl-CoA Synthetase

A substrate-level phosphorylation

A nucleoside triphosphate is made (ATPin plants/bacteria and GTP in animals)

Its synthesis is driven by hydrolysis of aCoA ester


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Succinate Dehydrogenase

An oxidation involving FAD Mechanism involves hydride removal by FAD and

a deprotonation

This enzyme is actually part of the electron

transport pathway in the inner mitochondrialmembrane

The electrons transferred from succinate toFAD (to form FADH2) are passed directly to

ubiquinone (UQ) in the electron transportpathway

Enzyme inhibited by malonate


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Fumarase

Hydration across the double bond

trans-addition of the elements of

water across the double bond Stereospecific reaction


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Malate Dehydrogenase An NAD+-dependent oxidation The carbon that gets oxidized is the one

that received the -OH in the previousreaction

This reaction is energetically expensive

Go' = +30 kJ/mol


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Reduced Coenzymes Fuel ATP

Production Acetyl-CoA + 3 NAD+ + Q + GDP + Pi +2 H20

HS-CoA + 3NADH + QH2 + GTP + 2 CO2 + 2 H+

Isocitrate Dehydrogenase 1 NADH=2.5 ATP -ketoglutarate dehydrogenase 1 NADH=2.5 ATP Succinyl-CoA synthetase 1 GTP=1 ATP Sunccinate dehydrogenase 1 QH2=1.5 ATP

Malate Dehydrogenase 1 NADH=2.5 ATP

Total of 10 ATPs gained from oxidation of 1 Acetyl-CoA


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Regulationof TCACycle


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TCA Cycle providesintermediates formany biosyntheticprocesses


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The Anaplerotic ReactionsThe "filling up" reactions

PEP carboxylase - converts PEP to oxaloacetate

Pyruvate carboxylase - converts pyruvate tooxaloacetate

Malic enzyme converts pyruvate into malate

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