Oxidative decarboxylation

Oxidative decarboxylation is a decarboxylation reaction caused by oxidation.

Organic chemistry

Lead tetraacetate converts carboxylic acids to alkenes. ^[1]

RCH₂CH₂CO₂H + Pb(O₂CCH₃)₄ → RCH=CH₂ + CO₂ + 2 HO₂CCH₃ + Pb(O₂CCH₃)₂

Biochemical context

Most are accompanied by α-ketoglutarate α-decarboxylation caused by dehydrogenation of hydroxyl carboxylic acids such as carbonyl carboxylic malic acid, isocitric acid, etc. ^[2]

Pyruvate is susceptible to oxidative decarboxylation to deliver the equivalent of the acetyl anion:

CH₃C(O)CO−2 → "CH₃CO⁻" + CO₂

This irreversible reaction is catalyzed by the pyruvate dehydrogenase complex. It consists of three enzymes: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), six cofactors: thiamine pyrophosphate (TPP), lipoamide, coenzyme A (CoA), flavin adenine dinucleotide (FAD), magnesium ion, and one co-substrate: nicotinamide adenine dinucleotide (NAD+). ^{[3] [4] [5] [6]} Pyruvate converts the thiazole ring of TPP to its hydroxyethyl derivative, concomitant with decarboxylation. With the catalysis of E2, TPP-CH(OH)CH₃ reacts with the S-S bond of lipoamide to produce thioester bond (acetyl dihydrolipoamide. The acetyl reacts with CoA-SH to give Acetyl-CoA and dihydrolipoamide. The latter is oxidized to lipoamide (with S-S bond) by FAD. ^[7]

Glycolysis and the citric acid cycle

Pyruvate, the product of glycolysis under aerobic conditions, is a metabolic branch point. As a preliminary to following the central path of aerobic metabolism from glycolysis to the citric acid cycle, we put pyruvate in perspective by considering its various possible fates. We also consider the broader context of common carboxylation and decarboxylation reactions in biochemistry.

References

1. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 1743, ISBN   978-0-471-72091-1
2. Dejun, Zhou (2012). Organic reaction mechanism. Chemical Industry Press.
3. Patel, MS; Korotchkina, LG (2003). "The biochemistry of the pyruvate dehydrogenase complex". Biochem Mol Biol Educ. 31: 5–15. doi:10.1002/bmb.2003.494031010156.
4. Staunton, J. Primary Metabolism (1978). A Mechanistic Approach. Oxford University Press.
5. Silverman, RB (2002). The Organic Chemistry of Enzyme-Catalyzed Reactions. Academic Press.
6. Yixian, Lv. Organic Chemistry 7th Edition.
7. Nelson, David L.; Cox, Michael M. (2005). Principles of Biochemistry (4th ed.). New York: W. H. Freeman. p. 571. ISBN   0-7167-4339-6.