Ornithine aminotransferase deficiency

Ramesh V, McClatchey Al, Ramesh N, Benoit LA, Berson EL, et al. 1988. Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and-nonresponsive forms of gyrate atrophy. Proc Natl Acad Sci USA 85 5777-5780. 

Arginine B i L Ornithine aminotransferase deficiency (gyrate atrophy)... 

A question of stability. Pyridoxal phosphate (PLP) is a coenzyme for the enzyme ornithine aminotransferase. The enzyme was purified from cells grovm in PLP-deficient media as well as from cells grown in media that contained pyridoxal phosphate. The stability of the enzyme was then measured by incubating the enzyme at 37°C and assaying for the amount of enzyme activity remaining. The following results were obtained. 

Decarboxylation of ornithine to putrescine by ornithine decarboxylase serves as a source of the polyamines spermidine and spermine. Ornithinemia results from deficiency of ornithine aminotransferase or ornithine... 

Table 12.1. Ornithine-6-aminotransferase deficiency (hyperornithinemia) (more than...

Because the proposed transfers of redox mediated by the metabolism of P5C can be catalyzed by several enzyme mechanisms, inborn deficiencies of any one of the mechanisms would not necessarily result in a total absence of P5C-mediated redox transfers. In fact, pathophysiologic manifestations may be limited to those tissues in which the deficient mechanism plays a major physiologic role. For example, in gyrate atrophy of the choroid and retina with absent ornithine aminotransferase, the pathology is restricted to ocular tissues. Within the proposed scheme for P5C-mediated redox transfers, this tissue specificity may be due to the absence or relative deficiency of proline oxidase and P5C synthase in ocular tissues (61). The proposed redox transfer mechanisms would then be deficient since there is no source of P5C. We can speculate that the deficiency in the transfer of cytosolic NADPH (Table H) is related to the pathogenesis of the ocular pathology. 

A (UsorAex hyperornithinemia of the retina and choroid with gyrate atrophy and progressive degeneration is due to the deficiency of the enzyme omithine-5-aminotransferase (OAT). OAT deficiency is inherited as an autosomal recessive disorder and illustrates the metabolic importance of ornithine, a nonprotein amino acid (Chapter 17). Ornithine participates either as a substrate or a product of five enzymatic reactions. Two biochemical mechanisms have been proposed to explain the pathophysiology of gyrate atrophy of the choroid and the retina. One is that a high ornithine concentration causes reduced formation of... 

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