Enzymes, decarboxylation glutamic acid

Enzymes that decarboxylate glutamic acid are widely distributed in bacteria [12). 

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. 

GABA synthesis inhibitors act on the enzymes involved in the decarboxylation and transamination of GABA. Glutamic acid decarboxylase (GAD), the first enzyme in GABA biosynthesis, is inhibited easily by carbonyl reagents such as hydrazines [e.g., hydrazinopropionic acid (4.164) or isonicotinic acid hydrazide (4.165)], which trap pyridoxal, the essential cofactor of the enzyme. A more specific inhibitor is allylglycine (4.166). All of these compounds cause seizures and convulsions because they decrease the concentration of GABA. 

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

In general, acidic proteinoids are more active than lysine-rich proteinoids for this reaction. Thermal poly(glutamic acid, threonine) and thermal Poly(glutamic acid, leucine) are the most active of these tested 20>. The activity is gradually decreased by progressive acid hydrolysis20. Compared with natural enzymes, the activity of proteinoid is weak. However the decarboxylation of pyruvic acid by proteinoid obeys Michaelis-Menten kinetics as expressed by the Lineweaver-Burk plot201. In this reaction a small amount of acetaldehyde and acetoin are formed in addition to acetic acid and C02 201. 

Canaline is the product of the hydrolytic cleavage of canavanine with the simultaneous formation of urea. Canaline is an ornithine analogue which also shows neurotoxicity in the adult sexta where it adversely affects central nervous system functions (jj ). It also is a potent inhibitor of vitamin B -containing enzymes (20-22). It forms a stable Schiff base with the pyridoxal phosphate moiety of the enzyme and drastically curtails enzymatic activity. Pyridoxal phosphate-containing enzymes are vital to insects because they function in many essential transamination and decarboxylation reactions. Ornithine is an important metabolic precursor for insect production of glutamic acid and proline (23). 

In addition to amino acid decarboxylation and racemization, PLP is a coenzyme for transamination— the transfer of an amino group from one compound to another. The enzymes that catalyze transaminations are called aminotransferases or transaminases. Many transaminations involve two compounds a-ketoglutaric acid and L-glutamic acid. 

Enzyme-catalyzed decarboxylation of glutamic acid gives 4-aminobutanoic acid (Section 18.2D). Estimate the pi of 4-aminobutanoic acid. 

Pharmacological evidence was obtained several years ago that indicated that tryptophan is decarboxylated to tryptamine by both animal and bacterial enzymes. More recent studies have failed to detect this reaction, but instead have shown decarboxylation to occur only after oxidation of the indole nucleus to yield 5-hydroxytryptophan. Decarboxylation of 5-hydroxytryptophan produces 5-hydroxytryptamine, serotonin, which has important, though incompletely defined functions in animal physiology. In some animal livers there is an enzyme that decarboxylates cysteic acid to taurine. Glutamic decarboxylase has been found in animal brain, where it is responsible for the formation of 7-aminobutyric acid. This product has been implicated in nervous function as an inhibitor of synaptic transmission. ... 

Degradation. One pathway of degradation is started by decarboxylation to histamine by the enzyme previously discussed. This is a minor pathway in terms of quantities of histidine metabolized. The major pathway in both animals and microorganisms retains the 5-carbon chain and leads to glutamic acid. Older work established that histidine degradation occurs only in the livers of animals, but this work was carried out only with crude preparations, and led to the publication and general acceptance of hypothetical schemes that have little relation to reactions found more recently. 

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