Lecture 34 Summary

Update for Fall 2009 in progress...

Oxidative phosphorylation.

The pyruvate dehydrogenase (PDH) complex

The PDH complex carries out the oxidative decarboxylation process that generates acetyl CoA from pyruvate. The PDH complex serves as the link between glycolysis and the citric acid cycle, and is required for oxidative metabolism. The activity of PDH involves three distinct enzymes, four activities, and five different cofactors (see BTS, pp.467-472).

Steps of the PDH complex:

(1) decarboxylation (E1, formation of hydroxyethyl-TPP)

(2) oxidation (transfer of acetyl group to lipoamide)

(3) transfer of acetyl group from acetyllipoamide to CoA)

(4) oxidation of dihydrolipoamide to lipoamide (E3, FAD, NAD⁺)

The α-ketoglutarate dehydrogenase complex, which participates in the citric acid cycle, shows a close resemblance to PDH complex.

The biochemistry of thiamine

Thiamine pyrophosphate (TPP), a key catalytic cofactor of the PDH complex, assists in decarboxylations of α-keto acids, and is a carrier of activated aldehyde moeities.

A hydrogen attached to the C2 carbon of the thiazole ring of TPP shows an unusually low pK_a.

Thiamine deficiency underlies the disorder beriberi.

Learning objectives

Page update in progress, 10-01-09

References

1. Staunton J. Primary Metabolism: A Mechanistic Approoach (1978, Oxford University Press)
2. Silverman RB. The Organic Chemistry of Enzyme-Catalyzed Reactions (Revised ed., 2002, Academic Press).