Ornithine mutases

Ethanolamine ammonia lyase, L-/ -lysine mutase, D-a-lysine mutase and ornithine mutase are representative of cobamide enzymes in which transfer of hydrogen occurs with cleavage of the C—N bond (Fig. 16). 

D-a-Lysine mutase and ornithine mutase catalyze the same type of reaction... 

Ornithine decarboxylase 342, 342s Ornithine mutases 871, 874 Oscillatoria 22 Osmate ester 393s Osmotic shock 417 Osteoarthritis 438 Osteoblasts 26, 441... 

Ornithine mutase D-Ornithine NHj D-f/zreo-2,4-Diaminovaleric acid... 

Figure 47-SO The major metabolic pathways for the use of ammonia by the hepatocyte. Solid bars indicate the sites of primary enzyme defects in various metabolic disorders associated with hyperammonemia /) carbamyl phosphate synthetase I, (2) ornithine transcarbamylase, (3) argininosuccinate synthetase, (4) argininosuccinate lyase, (5) arginase, (6) mitochondrial ornithine transport, (7) propionyi CoA carboxylase, (fi) methylmalonyl CoA mutase, (9) L-lysine dehydrogenase, and (10) N-acetyl glutamine synthetase. Dotted lines indicate the site of pathway activation (+) or inhibition ( ). (From Flannery OB, Hsia YE, Wolf 6. Current status of /lyperommofiemjo syndromes. Hepatology 1982 2 495-506,)...

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. 

Lysine 5,6-aminomutase (5,6-LAM) catalyzes the isomerization of D-lysine to 2,5-diaminohexanoic acid [180,181]. The mechanism proposed is analogous to that of D-ornithine amino mutase [228,229]. 5,6-LAM was predicted to be a base-off/His-on Bi2-dependent enzyme [230], as was recently conformed by the crystal structure [231]. 

Rate liver carbamoylphosphate synthetase I and ornithine transcarbamoyiase UDP-galactopyranose mutase... 

In biochemical parlance, these systems are called mutases, or sometimes isomerases. When Z = OH and Y = OH or NHj, the product eliminates an aldehyde and either HjO or NH3 so that the process is irreversible. Such systems sometimes are referred to as eliminases, dehydrases or ammonia-lyases. Examples of these various types of systems are shown by the first five examples in Figure 8.3, where (CoA)—S represents coenzyme A. It should be noted that the amino mutases, such as ornithine amino mutase, also require pyridoxal phosphate as a cofactor. 

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