Glutamate transamination

The reported molecular weight is about 110,000 and the enzyme has 2 mol pyridoxal phosphate per mol of enzyme. It is reasonable to assume that the aspartate formed during CAM metabolism is by glutamate transamination to oxalacetate. 

L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

In transamination an amine group is transferred from L glutamic acid to pyruvic acid An outline of the mechanism of transamination is presented m Figure 27 4... 

Most amino acids lose their nitrogen atom by a transamination reaction in which the -NH2 group of the amino acid changes places with the keto group of ct-ketoglutarate. The products are a new a-keto acid plus glutamate. The overall process occurs in two parts, is catalyzed by aminotransferase enzymes, and involves participation of the coenzyme pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin UJ. Different aminotransferases differ in their specificity for amino acids, but the mechanism remains the same. 

Write all the steps in the transamination reaction of PMP with a-ketoglutarate plus a lysine residue in the enzyme to give the PLP-enzyme inline plus glutamate. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Figure 7-4. Ping-pong mechanism for transamination. E—CHO and E—CHjNHj represent the enzyme-pyridoxal phosphate and enzyme-pyridoxamine complexes, respectively. (Ala, alanine Pyr, pyruvate KG, a-ketoglutarate Glu, glutamate).

Figure 28-3. Formation of alanine by transamination of pyruvate. The amino donor may be glutamate or aspartate. The other product thus is a-ketoglutarate or oxaloacetate.

Urea biosynthesis occurs in four stages (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2). 

Transamination channels a-amino acid nitrogen into glutamate. L-Glutamate dehydrogenase (GDH) occupies a central position in nitrogen metabolism. 

Alanine. Transamination of alanine forms pyruvate. Perhaps for the reason advanced under glutamate and aspartate catabolism, there is no known metabolic defect of alanine catabolism. Cysteine. Cystine is first reduced to cysteine by cystine reductase (Figure 30-7). Two different pathways then convert cysteine to pyruvate (Figure 30-8). 

These points have important functional implications. While neuronal glutamate may come from glucose via pyruvate, the Krebs cycle and transamination of alpha-oxoglutamate, it seems likely that most of the transmitter originates from the deamination of glutamine. After release, the high-affinity uptake sites (transporters)... 

The result is that the amino groups can be dumped out as alanine (the transamination product of pyruvate). In the liver and kidney, alanine is transaminated to yield pyruvate and glutamate. As in the Cord cycle, the pyruvate is converted to glucose by the liver and is shipped out. The glutamate is fed into the urea cycle-nitrogen disposal system to get rid of the excess nitrogen. 

The nitrogen from the pyrimidine bases is removed by transamination and dumped onto glutamate. The carbon skeleton ends up as C02. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

The biological importance of transamination was confirmed using 15N-labeling experiments (Tannenbaum and Shemin, 1950). 15N-leucine incubated with pig heart muscle gave highly labelled 15N-glutamate, evidence that leucine could be transaminated. Isotope experiments were then extended to the whole range of amino acids. 

The association between vitamin B6 deficiency and transamination emerged from 1945 when Schlenk and Fisher noted that pyridoxine-deficient rats had a diminished capacity for transamination. In the same year Gunsalus and his colleagues found transamination in Streptococcus faecalis depended on pydridoxal phosphate. The properties of the heat-stable component in purified glutamic-oxaloacetate transaminase were similar to those of pydridoxal phosphate. Later pyri-doxal phosphate was established as an essential coenzyme in many amino acid transformations. 

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