Abstract
Genetic analyses, involving backcross and F2 matings, demonstrate that the type I hyperprolinemia of PRO/Re mice is caused by an abnormal allele at a single locus designated pro-1. Mice homozygous for this allele (pro-1b/pro-1b) possess 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 K m (proline) for the Triton X-100 solubilized enzyme activities of PRO/Re and C57BL/6J liver mitochondria of 0.4 M and 2.9×10−3 M, respectively. C57BL/6J enzyme activity is inhibited by high substrate concentration. The activity of component 1 was not detected in other subcellular fractions 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.
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This investigation was supported by NIH Research Grants AM 14769 from the National Institute of Arthritis, Metabolic, and Digestive Diseases and CA 01074 from the National Cancer Institute, and by an allocation from NIH General Research Support Grant RR 05545 from the Division of Research Resources to the Jackson Laboratory. The Jackson Laboratory is fully accredited by the American Association of Laboratory Animal Care.
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Blake, R.L., Hall, J.G. & Russell, E.S. Mitochondrial proline dehydrogenase deficiency in hyperprolinemic PRO/Re mice: Genetic and enzymatic analyses. Biochem Genet 14, 739–757 (1976). https://doi.org/10.1007/BF00485338
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DOI: https://doi.org/10.1007/BF00485338