Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes.
We have recently shown that cytoplasmic malate dehydrogenase (MDH-s) from several non-human species catalyses the reduction of aromatic alpha-keto acids in the presence of NADH (Friedrich et al. 1987), an activity previously attributed to the enzyme aromatic alpha-keto acid reductase (KAR E.C.1.1.1.96). Here we present evidence that this also occurs in humans, and that the previously characterized human KAR is not the product of a genetically distinct locus. Human MDH-s and KAR activities co-migrate after starch gel electrophoresis, and electrophoretic variants of human MDH-s exhibited identical variation for KAR. Both enzymes show almost no electrophoretic variation among human populations of diverse origin. The reduction of aromatic alpha-keto acids is substantially inhibited by malate, the end-product of the MDH reaction. Antibodies raised against purified chicken MDH-s equally inhibited both MDH-s and KAR in chickens and humans. The bulk of the KAR activity in human blood appears to be due to MDH-s, with a minor fraction catalysed by LDH, as is the case in most other species studied. The previous assignment of a gene for KAR to human chromosome 12 in human/Chinese hamster somatic cell hybrids is questioned because interspecific hybrid bands of both MDH-s and LDH appear with slightly different mobility approximately midway between the human and hamster controls in somatic cell hybrid studies, and the meaning of this artifact is discussed. The discovery that MDH reacts with intermediate metabolites of phenylalanine and tyrosine has implications in relation to the mechanism by which mental retardation may be produced in phenylketonuria (PKU), and the effect of MDH inhibition on oxidative phosphorylation in the various tyrosinaemias is discussed.
D000429:Alcohol Oxidoreductases / Q000097:blood* / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology*; D006358:Hot Temperature; D006801:Humans; D006822:Hybrid Cells; D007527:Isoenzymes; D008291:Malate Dehydrogenase / Q000097:blood* / Q000235:genetics
D007527:Isoenzymes; D000429:Alcohol Oxidoreductases; D008291:Malate Dehydrogenase; C020060:diiodophenylpyruvate reductase