3-Oxoglutaric acid, hydrogenation

The second function, and the one pertinent to this section, is the decarboxylation of oxalosuccinic acid to 2-oxoglutaric acid. This is simply a biochemical example of the ready decarboxylation of a P-ketoacid, involving an intramolecular hydrogen-bonded system. This reaction could occur chemically without an enzyme, but it is known that isocitric acid, the product of the dehydrogenation, is still bound to the enzyme isocitrate dehydrogenase when decarboxylation occurs. 

Felfoldi, K., Szori, K., Bartok, M. (2003) Heterogeneous as5nnmetric reactions. Part 35. Enantioselective hydrogenation of 2-oxoglutaric acid over cinchona modified Pt/Al203 catalysts, A/ip/. Catal. A. Gen. 251, 457-460. 

Here then the distinction between substrates and co-enzymes can only be made in terms of the quantities involved. These enz)une systems oxidatively decarboxylate a large amount of 2-oxoglutaric acid to succinic acid. The small amount of co-enzyme A acts over and over again and the small amount of co-enz)rme I (NAD) is constantly being re-oxidised by another set of enzymes and so acts over and over again to remove hydrogen from the 2-oxogIutarate. 

Hydrogenations of Diethyl 2-Oxoglutarate (I) and 2-Methyl-4-benzaloxazoline (3) with RNi or RNis Treated with (S)-Amino Acids... 

The original details of the influence of optically active additives on catalytic reactions were reported by Isoda et al. Hydrogenation of C=0 and C=N bonds in diethyl 2-oxoglutarate and diethyl 2-oximinoglutarate were carried out in the presence of modifier compounds (camphor, bomeol, amino acids) in situ at elevated hydrogen pressures and temperatures. 

Table 4.1. Enantioselective hydrogenation of the C=0 bond in diethyl 2-oxoglutarate to diethyl 2-hydroxyglutarate, of the C=N bond in diethyl 2-oximmoglutarate to diethyl glutamate, and of the C=C bonds in 2-acetamidocmnamic acid to phenylalanine on Raney nickel catalysts, modified with optically active ketones, alcohols and amino acids (according to mainly Isoda et al. ).

This is the first oxidative step and is catalysed by isocitrate dehydrogenase. While the substrate is attached to the enzyme two hydrogen atoms are removed, and transferred to NAD, a molecule of CO2 is also lost and the five-carbon dicarboxylic acid, 2-oxoglutarate, is formed. 

CO2 and the generation of reduced hydrogen carriers. A number of cycle intermediates may be used in biosynthetic pathways. Oxaloacetate and 2-oxoglutarate may be converted into aspartate and glutamate respectively by amino transfer reactions (Section 16.1) and thereby be employed as sources of these amino acids for protein synthesis. 

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