Ornithine, transamination reactions

In some cases, the function of the metal ion is more to deactivate alternative sites of reaction than to activate a particular atom towards attack by an electrophile. A good example of this is seen in the transamination reaction of ornithine (5.12) with urea. Co-ordination of the ornithine to copper(n) results in the formation of a five-membered chelate ring, leaving the amino group of the 3-aminopropyl substituent as the most nucleophilic site in the complex. Reaction of this complex with urea results in a transamination process and the formation of the copper(n) complex of the substituted urea, which is the amino acid citrulline (5.13) (Fig. 5-20). The complex may be demetallated to yield the free amino acid in respectable yields. 

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. 

Other methods can also be used for driving the transamination reaction to produce amino adds in high yields. For example, if L-lysine or L-ornithine are used as the donor in the two-enzyme process shown in Fig. 12.7-9, the cyclization of the aldehyde is strongly favored, creating an essentially irreversible reaction that can lead to high yields of a desired amino add from the corresponding 2-keto-... 

Ornithine is an amino acid. However, it is not incorporated into proteins during the process of protein synthesis because no genetic codon exists for this amino acid. Although ornithine is normally regenerated by the urea cycle (one of the products of the arginase reaction), ornithine also can be synthesized de novo if needed. The reaction is an unusual transamination reaction catalyzed by ornithine aminotransferase under specific conditions in the intestine (Fig. 38.14). The usual direction of this reaction is the formation of glutamate semialdehyde, which is the first step of the degradation pathway for ornithine. 

Arginine is cleaved by arginase to form urea and ornithine. If ornithine is present in amounts in excess of those required for the urea cycle, it is transaminated to glutamate semialdehyde, which is reduced to glutamate. The conversion of an aldehyde to a primary amine is a unique form of a transamination reaction and requires pyridoxal phosphate (PLP). 

The conversion of ornithine to A -pyrroline -carboxylate is better understood, since the transamination reaction by which this occurs has been studied in some detail with Neurospora 121) and liver extracts 122). The equilibrium of the transaminase reaction with a-ketoglutaric acid as amino group acceptor favors A -pyrroline-5-carboxylate formation about 90% of the ornithine is decomposed. 

The discovery of the transamination reaction supplies a pathway whereby ornithine can be formed from glutamic acid or any other precursor of glutamic semialdehyde. 

Arginine, via three reactions of the urea cycle, can be derived from ornithine, which is produced by transamination of glutamate semialdehyde. 

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). 

The transamination of P-aminoisobutyrate to form methylmalonate semialdehyde requires pyridoxal phosphate as a cofactor. This reaction is similar to the conversion of ornithine to glutamate y-semialdehyde. Then NAD+ serves as an electron acceptor for the oxidation of methylmalonate semialdehyde to methylmalonate. The conversion of methylmalonate to methylmalonyl CoA requires coenzyme A. The final reaction, in which methylmalonyl CoA is converted to succinyl CoA, is catalyzed by methylmalonyl CoA mutase, an enzyme that contains a derivative of vitamin B12 as its coenzyme. 

Ornithine Biosynthesis. Two reaction sequences leading to ornithine synthesis from glutamic acid have been described. In Neurospora and the yeast Tondopsis utilis the sequence involves the simple transamination of glutamic semialdehyde (IV). The reaction proceeds much... 

PLP-mediated transamination of the glutamate 5-semialdehyde carbonyl group hy reaction with glutamate then gives ornithine, which is converted to arginine in the urea cycle, as discussed previously in Section 20.3 (Figure 20.5). 

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