Glutamic acid semialdehyde

There is a. ccTtain amount of evi(l(Mic( that tlu semialdehydo of glutamic acid is the intermediate formy the loss of the 5-araino group of ornithine. This evidence is the isolation of what was presumed to be the 2,4-dinitrophenylhydrazone of the semialdehyde upon partial oxidation of proline by the cyclophorase system. The glutamic acid semialdehyde can be expected to condense readily to pyrroline carboxylic acid, and reduction of this compound would yield proline (Fig. 2). 

In plants and in most bacteria, 5-aminolevulinic acid is produced by an alternative pathway involving tRNA-bound glutamate and two enzymatic steps catalyzed by glutamyl-f-RNA reductase and by glutamate-1-semialdehyde-2,1-aminomutase (7, 8). 

Succinic semialdehyde was not detectable. Poly-7-glutamic acid showed a 54 % loss of glutamic acid a,/3-diaminopropionic acid was not determined, but no a,7-diaminobutyric acid could be found. The hydrolyzate gave a strong positive test for succinic semialdehyde, and the ammonia in the hydrolyzate indicated that the lost glutamic acid had undergone reaction as expected. 

Reductive aminations also occur in various biological pathways. In the biosynthesis of the amino acid proline, for instance, glutamate 5-semialdehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

The individual steps involved in the conversion of glutamate into ALA are shown in Scheme 6 [1,2,13]. First the glutamate is converted by an ATP-depen-dent ligase into a RNA ester 18, which appears to be the same as the gluta-myl- RNA used for protein synthesis in the plant chloroplast. This gluta-rnyl- RNA is then reduced by an NADPH-dependent reductase to glutamate 1-semialdehyde 19. As expected of an a-amino aldehyde, 19 is not particularly stable under neutral or basic conditions but can be isolated under acidic conditions, under which it cyclises to the corresponding lactol [2]. 

Figure 12-4. Gamma-aminobutyric acid metabolic interactions. GA = glutaminase GABA = y-aminobutyric acid GABA-T = GABA a-oxaloglutarate transaminase GAD = glutamic acid decarboxylase GS = glutamic synthetase NAD+ = nicotinamide adenine dinucleotide PP = pyridoxal phosphate (vitamin B6) SSA = succinic semialdehyde SSADH = succinic semialdehyde dehydrogenase GHB = y-hydroxybutyric acid GBL = y-butyrolactone.

GABA-T utilizes pyridoxal as the cofactor in the transamination reaction (Fig. 12-7A). Pyridoxal 5-phosphate (Vitamin B6, the cofactor) forms a Schiff base with GABA s NH2 group. The adjacent C-H bond has its proton abstracted by the enzyme reprotonation results in the tautomeric Schiff base, which on hydrolysis affords succinic semialdehyde and pyridoxamine. The pyridoxamine then forms a Schiff base with the carbonyl of a-ketoglutarate, reversing the steps, whereby hydrolysis of the tautomeric base yields l-glutamic acid, and the pyridoxamine, which has given up its NH2 function, reverts to the cofactor aldehyde form to repeat the cycle. 

GABA-AT 7-aminobutyric acid aminotransferase GSA glutamate-1 -semialdehyde... 

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