Comparison of ornithine metabolism in hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts.
We measured L-ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (McKusick 22270) cells in which there is an ornithine transport abnormality at the plasma membrane. Net uptake of ornithine is not abnormal in intact HHH cells. Ornithine oxidation was depressed in HHH and gyrate atrophy cells but not in lysinuric protein intolerance cells; the latter finding suggests there is no significant mitochondrial defect in lysinuric protein intolerance cells. Since HHH cells have intact ornithine aminotransferase, impaired oxidation is compatible with deficient penetration of ornithine into mitochondria in this disease. We could not demonstrate a gene dosage effect in oxidation values.
Botschner
J
J
Medical Research Council Genetics Group, McGill University-Montreal Children's Hospital, Quebec, Canada.
Smith
D W
DW
Simell
O
O
Scriver
C R
CR
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D000641:Ammonia / Q000097:blood; D002956:Citrulline / Q000031:analogs & derivatives / Q000652:urine; D005347:Fibroblasts / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008239:Lysine / Q000652:urine; D009952:Ornithine / Q000097:blood / Q000378:metabolism*; D009953:Ornithine-Oxo-Acid Transaminase / Q000172:deficiency; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D013577:Syndrome
D011506:Proteins; C001352:homocitrulline; D002956:Citrulline; D000641:Ammonia; D009952:Ornithine; D009953:Ornithine-Oxo-Acid Transaminase; D008239:Lysine