Oxidative decarboxylation

An oxidative decarboxylation is a chemical reaction in which the carboxy group (–COOH) of a carboxylic acid is split off as carbon dioxide (CO ₂ ) and the remaining molecule is oxidized . This is how most of the carbon dioxide is created that living things exhale or otherwise give off. Three different oxidative decarboxylations occur during cell respiration . The substrates are pyruvate , which comes from glycolysis , as well as isocitrate and α-ketoglutarate as metabolites in the citric acid cycle . The oxidation takes place here by transferring two hydrogen atoms to nicotinamide adenine dinucleotide (NAD ⁺ ). The hydrogen is the respiratory chain where it is separated ultimately lead to reduction of oxygen used.

Involved Enzymes and Coenzymes

The oxidative decarboxylation of pyruvate and α-ketoglutarate is catalyzed by large multi-enzyme complexes that consist of many copies of three enzymes: a decarboxylase , an oxidoreductase, and a dehydrogenase . Thiamine pyrophosphate , coenzyme A and NAD ^{+ are} required as coenzymes , and FAD and lipoic acid as prosthetic groups . The enzymatic conversion of pyruvate to acetyl-CoA is catalyzed by the pyruvate dehydrogenase complex . α-Ketoglutarate is converted to succinyl-CoA in the α-ketoglutarate dehydrogenase complex . With the exception of the respective dehydrogenase, which determines the substrate specificity (for pyruvate or α-ketoglutarate), the two enzyme complexes are very similar to each other, which indicates a common evolutionary origin. In contrast, the oxidative decarboxylation of isocitrate is catalyzed by a single enzyme, isocitrate dehydrogenase .

Process of the oxidative decarboxylation of pyruvate

Representation of the oxidative decarboxylation of pyruvate (R = H) or α-ketoglutarate (R = CH ₂ –CH ₂ –COO ^- ). Thiamine pyrophosphate (TPP) and liponamide are only shown in sections. Please see text for details.

The process of oxidative decarboxylation is shown using the example of pyruvate (see scheme in the picture, R = H):

• The pyruvate attaches to thiamine pyrophosphate (TPP), a derivative of vitamin B ₁ . Then the acid group of the pyruvate is split off as CO ₂ , so that hydroxyethyl-TPP is formed (step A in the scheme). This is catalyzed by the pyruvate dehydrogenase component (E ₁ ) .

• The hydroxyethyl group is transferred to liponamide . The result is a thioester , acetyl dihydroliponamide, so the disulfide group serves as the oxidizing agent. The TPP is regenerated (step B ). This reaction is also catalyzed by the pyruvate dehydrogenase component.

• The acetyl group is transferred to coenzyme A, acetyl-CoA is formed. This step is catalyzed by dihydrolipoyl transacetylase (E ₂ ) . From a chemical point of view, this is a transesterification (step C ).

• The liponamide is regenerated by a dihydrolipoyl dehydrogenase (E ₃ ) by oxidizing the dihydroliponamide with enzyme-bound FAD to liponamide (step D ). However, FAD is not covalently bound to enzymes.

• Finally, FAD is regenerated by reducing NAD ⁺ to NADH by the same dehydrogenase (step E ). The electron transfer potential is increased from FADH ₂ to NAD ⁺ because it is associated with the enzyme.

The balance of oxidative decarboxylation for pyruvate is:

${\displaystyle \mathrm {CH_{3}COCOOH+NAD^{+}+CoA{\text{-}}SH\longrightarrow CH_{3}CO{\text{-}}SCoA+NADH+H^{+}+CO_{2}} }$

Examples from organic chemistry

In organic chemistry in general, oxidative decarboxylation refers to a reaction in which carbon dioxide is split off from a carboxylic acid with oxidation of the carbon chain. This can be done, for example, by heating or by oxidation with lead tetraacetate ( Kochi reaction ). In the Hunsdiecker reaction , the oxidative decarboxylation takes place via silver salts.

literature

• Jeremy M. Berg, Lubert Stryer, and John L. Tymoczko: Biochemistry . Spectrum Academic Publishing House; 6th edition 2007; ISBN 3827418003 ; Pp. 533-538.
• Joachim Rassow , Karin Hauser, Roland Netzker and Rainer Deutzmann: Biochemistry . Thieme Verlag Stuttgart; 2nd edition 2008; ISBN 978-3-13-125352-1 ; Pp. 104-109.

Web links

Wikibooks: Pyruvate Dehydrogenase Complex  - Learning and Teaching Materials

Wikibooks: α-Ketoglutarate Dehydrogenase  - Learning and Teaching Materials

Individual evidence

1. ^ Albert L. Lehninger, David L. Nelson, Michael M. Cox: Principles of Biochemistry . 2nd ed., Spektrum, Heidelberg / Berlin / Oxford 1994, pp. 522-525 and 530f.
2. ↑ Rassow et al. Biochemistry , p. 105.
3. ↑ Berg et al Biochemistry ; P. 538.
4. ^ ^{A b} Hans Peter Latscha, Uli Kazmaier and Helmut Alfons Klein: Organic Chemistry: Chemistry-Basiswissen II ; 5th edition. Springer Verlag, Berlin 2002; ISBN 3-540-42941-7 ; P. 257.