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I. Overview
The tricarboxylic acid cycle or TCA cycle, also known as the Krebs
cycle or citric acid cycle, is an important component in metabolism
It is the converging point where oxidative metabolism of
carbohydrates, amino acids, and fatty acids occurs
These compounds are converted to CO2 and H2O
This oxidation facilitates the production of ATP, thus, an energy source
in most animals
TCA cycle occurs exclusively in the mitochondria and is in close
proximity to reactions of electron transport
The cycle is aerobic in nature (O2 required as final electron acceptor)
TCA cycle also involved in the formation of glucose from some amino
acids and in formation of building blocks for synthesis of some amino
acids and heme
Intermediates of the cycle can also be produced via catabolism of
some amino acids
Oxidative decarboxylation
of pyruvate
Pyruvate (product of
aerobic glycolysis) is taken
to the mitochondrion prior
to decarboxylation by a
pyruvate transporter
Pyruvate then converted to
acetyl CoA by pyruvate
dehydrogenase complex
(multienzyme complex)
see figure
thiamine pyrophosphate
lipoic acid
coenzyme A
FAD
NAD+
Isomerization of citrate
G.
Oxidation of succinate
Hydration of fumarate
I.
Oxidation of malate
Malate is oxidized to
oxaloacetate in the presence of
malate dehydrogenase (see
figure)
Reaction affords the third and
final NADH of the cycle
By way of review, the PDH complex is inhibited by acetylCoA and NADH and activated by non-acetylated CoA
(CoASH) and NAD+.
The pyruvate dehydrogenase activities of the PDH complex
are regulated by their state of phosphorylation.
This modification is carried out by a specific kinase (PDH
kinase) and the phosphates are removed by a specific
phosphatase (PDH phosphatase).
The phosphorylation of PDH inhibits its activity and,
therefore, leads to decreased oxidation of pyruvate. PDH
kinase is activated by NADH and acetyl-CoA and inhibited by
pyruvate, ADP, CoASH, Ca2+ and Mg2+.
The PDH phosphatase, in contrast, is activated by Mg 2+ and
Ca2+.
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