ARGININE-GLYCINE TRANSAMIDINASE IN BOVINE NEURORETINA AND PIGMENT EPITHELIUM

Gyrate atrophy (GA) patients exhibit chorioretinal degeneration and histologic muscle abnormalities. Due to autosomal recessive deficiency of ornithine aminotransferase they accumulate ornithine to levels, which are 10× normal and well above the K, of arginine-glycine transamidinase of rat kidney. We have previously shown inadequate synthesis of guanidinoacetate and low creatine concentration in plasma, urine, erythrocytes, and muscle tissue of GA patients. Supplementary creatine corrected the atrophic muscle pathology but the chorioretinal atrophy continued. We alleged that this discrepancy was due to ineffective transport of creatine across the blood-eye barrier and sought for synthesis of guanidinoacetate in ocular tissues. We developed a new assay for measuring the arginine-glycine transamidinase activity in bovine eye tissues with a new assay based on the detection of formed guanidinoacetate with alkaline ninhydrin reaction. We found transamidinase activity only in the neuroretina (NR) and retinal pigment epithelium (RPE). The pH optimum was 7.5 in NR and 7.9 in RPE and the apparent Km for arginine was 1.10 in NR and 4.96 mM in RPE, and for glycine 1.03 and 0.95 mM, respectively. Our results indicate that a potential energy-rich phosphagen compound can be formed in eye tissues. Reduction of the ornithine concentration in ocular tissues can possibly enable the transamidination also in gyrate atrophy.