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Gyrate Atrophy of the Choroid and Retina with Hyperornithinemia: Characterization of Mutant Liver L-ornithine:2-oxoacid Aminotransferase Kinetics

Overview
Journal J Clin Invest
Specialty General Medicine
Date 1981 Jun 1
PMID 7240420
Citations 6
Authors
I Sipila
O Simell
J J ODonnell
Affiliations
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Abstract

Deficient activity of L-ornithine:2-oxoacid aminotransferase is associated with gyrate atrophy of the choroid and retina with hyperornithinemia, an autosomal recessive disease leading to blindness. Liver tissue from two patients contained trace activity of the enzyme. The Michaelis (Km) value of the mutant enzyme for ornithine was 200 mM, 50-fold higher than normal, but increasing the concentrations of alpha-oxoglutarate and pyridoxal 5'-phosphate to 10 times those giving maximal activity of the normal enzyme had no effect on the mutant enzyme. Substrate inhibition of the mutant could not be demonstrated at 1,000 mM ornithine concentration, whereas ornithine concentrations above 70 mM inhibited the normal enzyme. The data suggest that the abnormal L-ornithine:2-oxoacid aminotransferase in the two patients studied has an altered binding site for ornithine.

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Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy.

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References
1.
Simell O, Takki K . Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet. 1973; 1(7811):1031-3. DOI: 10.1016/s0140-6736(73)90667-3. View
2.
Sipila I, Simell O, Arjomaa P . Gyrate atrophy of the choroid and retina with hyperornithinemia. Deficient formation of guanidinoacetic acid from arginine. J Clin Invest. 1980; 66(4):684-7. PMC: 371642. DOI: 10.1172/JCI109905. View
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Takki K . Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol. 1974; 58(1):3-23. PMC: 1042586. DOI: 10.1136/bjo.58.1.3. View
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Trijbels J, Sengers R, BAKKEREN J, De Kort A, Deutman A . L-Ornithine-ketoacid-transaminase deficiency in cultured fibroblasts of a patient with hyperornithinaemia and gyrate atrophy of the choroid and retina. Clin Chim Acta. 1977; 79(2):371-7. DOI: 10.1016/0009-8981(77)90431-4. View
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Kennaway N, Weleber R, Buist N . Gyrate atrophy of choroid and retina: deficient activity of ornithine ketoacid aminotransferase in cultured skin fibroblasts. N Engl J Med. 1977; 297(21):1180. DOI: 10.1056/nejm197711242972116. View