Mitochondrial proline dehydrogenase deficiency in hyperprolinemic PRO/Re mice: genetic and enzymatic analyses.
Genetic analyses, involving backcross and F2 matings, demonstrate that the type I hyperprolinemia of PRO/Re mice is caused by an abnormal allelet at a single locus designated pro-1. Mice homozygous for this allele (pro-1b/pro-1b) posses a deficiency in the activity of component 1 of mitochondrial proline dehydrogenase. In liver mitochondria of normal C57BL/6J mice, two proline dehydrogenase activity components are demonstrable by electrophoretic resolution of Triton X-100 solubilized extracts. In mitochondria of PRO/Re mice, the activity of component 1 is not readily detectable. Residual proline dehydrogenase activity in PRO/Re mitochondria appears, therefore, to be due in large measure to activity component 2 which is more stable to incubation at 40 C, exhibits slower electrophoretic mobility, and is less reactive to menadione. Kinetic analyses demonstrate a Km (proline) for the Triton X-100 solubilized enzyme activities of PRO/Re and C57BL/6J liver mitochondria of 0.4 M and 2.9 X 10(-3) M, respectively. C57BL/6J enzyme activity is inhibited by high substrate concentration. The actins of PRO/Re liver obtained by differential centrifugation. Abnormal control of respiratory chain function in PRO/Re mitochondria appears to involve primarily proline oxidation, as indicated by the level of activity of several inner membrane enzymes.
D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D005796:Genes; D006358:Hot Temperature; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000648:ultrastructure; D010105:Oxygenases / Q000172:deficiency*; D011392:Proline / Q000097:blood / Q000378:metabolism*; D013045:Species Specificity; D014812:Vitamin K / Q000494:pharmacology
D014812:Vitamin K; D011392:Proline; D010105:Oxygenases; D000594:Amino Acid Oxidoreductases