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Biochem 5-21
Biochemistry: Aerobic Respiration - The Citric Acid Cycle
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Undergraduate 3
04/30/2010

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Term
The citric acid cycle
Definition
- a series of reactions associated with mitochondria to produce some ATP and a lot of reduced nucleotides
- AKA the TCA cycle and Krebs cycle (Krebs was knighted and given the Nobel prize for his work on the cycle)
Term
Summary Reaction of TCA
Definition
Acetyl-CoA + 3 NAD + FAD + GDP + Pi + 2 H20 ----> 2 CO2 + 3 NADH + FADH2 + CoASH + GTP
Term
Mitochondrial ultrastructure
Definition
**TCA cycle - Matrix
**Succinate deHase - Cristae M.
** Electron Transport - Cristae M.
**PDH Complex - Inner membrane/matrix
Term
Overview of TCA Cycle
Definition
**- complete oxidation of pyruvate to CO2
- reduction of nucleotide electron carriers
- production of some ATP
- regeneration of OAA
Term
Enzymes of the TCA
Definition
**- succinate dehydrogenase uses FAD
- pyruvate dehydrogenase, isocitrate dehydrogenase, alpha-ketogluterate dehydrogenase, and malate dehydrogenase all involve NADH
Term
Pyruvate dehydrogenase
Definition
- decarboxylates pyruvate
- promotes entry of pyruvate into cycle via formation of acetyl-CoA
- Subjected to complex regulation
- complex of three separate enzymes
Term
Pyruvate dehydrogenase complex
Definition
kinase phosphorylates serine which inactivates PDH
**phosphorylated serine
Term
mechanism for the oxidative decarboxylation of pyruvate
Definition
1. pyruvate loses CO2 and HETPP is formed
2. Hydroxyethyl group is transferred to lipoic acid and oxidized to form acetyl dihydrolipoamide
3. acetyl group is transferred to CoA
4. Dihydrolipoamide is reoxidized
Term
Two modes of regulation of pyruvate dehydrogenase
Definition
1. allosteric regulation
2. covalent modification
Term
allosteric regulation of pyruvate dehydrogenase
Definition
- inhibited by ATP, acetyl-coA, and NADH
- activated by AMP, CoASH, and NAD
Term
Covalent modification of pyruvate dehydrogenase
Definition
**- phosphorylation of E1 (PDH) - inactivation
**- modulate PDH protein kinase
Term
Citrate synthase
Definition
- allows entry of acetyl units via condensation with oxaloacetate to form citrate
1. regulation
- acetyl-CoA/OAA stimulate
- citrate inhibits
- succinyl-CoA inhibits
- high NADH and ATP ratios inhibit
Term
isocitrate dehydrogenase
Definition
- oxidation of isocitrate to alphaketogluterate is accompanied by reduction of NAD and release of CO2
1. regulation is ATP/NADH inhibit
ADP and NAD stimulate
oxalosuccinate is an intermediate
Term
alphaketogluterate dehydrogenase
Definition
- oxidation of alpha ketogluterate to succinyl-CoA is accompanied by the reduction of NAD and release of CO2
- succinyl-CoA and NADH inhibit
Term
Succinyl-CoA synthetase
Definition
** ATP is synthesized via nucleoside diphosphate kinase
- high-energy CoA thioester is cleaved to form succinate
- energy is conserved in substrate level phosphorylation of GDP
Term
succinate dehydrogenase
Definition
- succinate is oxidized to fumarate introducing a trans double bond
-FAD is reduced to FADH2
1. Regulation
- succinate, ATP and Pi activate
- OAA inhibits
Term
Malate dehydrogenase
Definition
- the final reaction of the TCA cycle
- oxidized to regenerate oxaloacetate and NAD is reduced to NADH
- forward reaction is not favorable but is pulled forward by the depletion of OAA
Term
Notes on TCA
Definition
- continues carbohydrate oxidation started in glycolysis all the way from pyruvate to CO2
- oxidation of the other energy-rich carbon substances like acetyl-coa from oxidation of fatty acids
- TCA is amphibolic - supply intermediates for other process
- TCA is anapleurotic - regenerate acetyl-acceptor
Term
cumulative summary for glycolysis/TCA
Definition
- both will stop unless oxidized nucleotides are regenerated
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