Histidine transamination

Non-essential amino acids are those that arise by transamination from 2-oxoacids in the intermediary metabolism. These belong to the glutamate family (Glu, Gin, Pro, Arg, derived from 2-oxoglutarate), the aspartate family (only Asp and Asn in this group, derived from oxaloacetate), and alanine, which can be formed by transamination from pyruvate. The amino acids in the serine family (Ser, Gly, Cys) and histidine, which arise from intermediates of glycolysis, can also be synthesized by the human body. 

Decarboxylation, or loss of the a-carboxyl group as C02, is another reaction common to most amino acids. It, too, requires pyridoxal phosphate as a coenzyme. Decarboxylation reactions are irreversible. For example, see Figure 20.5, which shows the decarboxylation of histidine to produce histamine. Table 20.6 lists transamination and decarboxylation products of some representative amino acids. 

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. 

Because transamination reactions are reversible, it is theoretically possible for all amino acids to be synthesized by transamination. However, experimental evidence indicates that there is no net synthesis of an amino acid if its a-keto acid precursor is not independently synthesized by the organism. For example, alanine, aspartate, and glutamate are nonessential for animals because their a-keto acid precursors (i.e., pyruvate, oxaloacetate, and a-ketoglutarate) are readily available metabolic intermediates. Because the reaction pathways for synthesizing molecules such as phenylpyruvate, a-keto-/Thydroxybutyrate, and imidazolepyruvate do not occur in animal cells, phenylalanine, threonine, and histidine must be provided in the diet. (Reaction pathways that synthesize amino acids from metabolic intermediates, not only by transamination, are referred to as de novo pathways.)... 

The pH dependence of the kinetics of histidine decarboxylase (127) demonstrates that the histidine is zwitterionic when it binds to the enzyme. The extra proton on nitrogen must, of course, be removed before the Schiff base is formed. The carboxylate of Glu-197 at the active site may accept this proton. In turn, this same group may then be responsible for proton donation to the Schiff base following decarboxylation. This is consistent with the occurrence of retention of configuration in the overall replacement of-C02 by -H (128) and with studies of enzymes altered at Glu-197 (129). When Glu-197 is replaced by Asp, the protonation that follows decarboxylation occasionally occurs on the pyruvate side, thus giving rise to decarboxylation-dependent transamination (129). 

The above general mechanism for non-enzymic, pyridoxal-catalysed processes was derived mainly from a study of transamination reactions. Nevertheless, non-enzymic, pyridoxal-catalysed decarboxylations have been reported, for example, that of histidine to histamine. The following pyridoxal-catalysed, non-enzymic decarboxylations of a-aminoisobutyric acid (R = = GHg), a-methylserine (R = GHjOH R = GHg) and... 

The amino acids of animal tissue are involved in other reactions (1) oxidative deamination (2) non-oxidative decarboxylation (3) transamination (4) protein synthesis. Oxidative deamination is important only with respect to L-glutamate, which can be converted to 2-oxogJutarate and ammonia by glutamate dehydrogenase. Decarboxylation is confined to a few amino acids in animal tissue, notably glutamate, histidine, and (after hydroxylation) tryptophan and phenylalanine. In all cases, the products are potent pharmacological agents discussed under autocoid metabolism. Serine is also decarboxylated to ethanolamine, an important reaction which is referred to later in connection with transamination. 

Deamination removal of the amino group (-NH ) from a chemical compound (usually an amino acid). MetaboUcally, D. may occur by a) oxidative D. of amino acids to ketoacids and ammonia by Flavin enzymes (see) and pyridine nucleotide enzymes (see Amino acids, Table 3) b) Transamination (see) in which an amino group is transferred fiom an amino to a keto compound, and c) removal of ammonia from a compound, leaving a double bond, e.g. the D. of L-aspartate to marate, and the D. of histidine to urocanic acid. IVansamination is important in the synthesis of amino acids from tricarboxylic acid cycle intermediates the reverse reactions feed excess amino acids into the tricarboxylic acid cycle for oxidation. 

Imidazolone propionate hydrolase catalyzes the enzymatic cleavage of the imidazole ring to yield formi-minoglutamate. The rat liver enzyme has been partially purified. In addition to the enzymic conversion, two nonenzymic spontaneous reactions yield N-formyl-isoglutamine and 4-oxoglutamic acid. In addition to the oxidative pathways for histidine, there exist three other pathways for its use protein synthesis, decarboxylation to yield histamine (see Inflammation), and transaminase. The activity of histidine pyruvic transamination in rat liver is three times that of histidase. The product of the transaminase reaction is imidazole pyruvic acid, which in turn is converted to imidazole acetic acid. 

Brief reference will be made to the following papers which have appeared since this chapter was written. Partially purified Neurospora L-serine dehydrase has been studied. Both L-serine and L-threonine appear to be deaminated by the same enzyme. The enzymatic pathway of histidine degradation in liver has been investigated. Soluble gluta-minase I has been prepared. Additional eiddence for the Avide scope of transamination has appeared. The presence of an ornithine-a-keto-glutarate transaminase in neurospora has been demonstrated. Transamination of non-a-amino acids has been demonstrated in brain in... 

The mechanism of the deamination and reamination of the a-amino group of histidine does not appear to be by the usual enzyme systems. This amino acid exhibits virtually no susceptibility to transamination by heart, liver, or kidney, and the two isomers, also, are poorly attacked by their respective amino acid oxidases. ... 

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