Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003969 (vitamin C deficiency)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver microsomal cytochrome P-450 is significantly reduced in ascorbic acid-deficient guinea pigs and studies are presented on the biochemical basis for this effect. The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthetase. ALA dehydratase and ferrochelatase, were not significantly reduced in livers from ascorbic acid-deficient animals. In addition, there was no significant difference in the amount of "mitochondrial heme" in normal and ascorbic acid-deficient livers. However, ascorbic acid deficiency did affect induction with diethyl-1,4-dihydro-2,4,6-trimethylpyridine-3,5-dicarboxylate; a 6-fold increase in ALA synthetase activity occurred in liver homogenates prepared from normal animals in contrast to no significant increase in homogenates prepared from ascorbic acid-deficient animals. Multiple forms of cytochrome P-450 exist in guinea-pig microsomes as has been demonstrated in microsomes from other species. Separation of 44,000 to 60,000 dalton polypeptides (molecular weight region for the various forms of cytochrome P-450) by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed quantitative differences in the polypeptides from normal and ascorbic acid-deficient microsomes. Ascorbic acid-deficient microsomes consistently demonstrated reductions in three polypeptide bands (molecular weight 44,000, 52,000 and 57,000) and increases in two polypeptide bands (54,000 and 55,000) compared with normal microsomes. Evidence that these polypeptides are cytochrome P-450 was obtained from heme staining with tetramethylbenzidine and from induction studies with phenobarbital and 3-methylcholanthrene. The results indicate that ascorbic acid deficiency does not affect the availability of heme for cytochrome P-450 synthesis and the effect of ascorbic acid may be on the apoprotein moiety of cytochrome P-450.
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PMID:Ascorbic acid and cytochrome P-450. 63 74

There is increasing evidence that the liver microsomal drug metabolizing system is affected by various vitamins such as ascorbic acid, riboflavin, and alpha-tocopherol. In regard to ascorbic acid deficiency there is a decrease in the quantity of hepatic microsomal electron transport components such as cytochrome P-450 and NADPH-cytochrome P-450 reductase, as well as decreases in a variety of drug enzyme reactions such as N-demethylation, O-demethylation, and steroid hydroxylation. In addition, young animals given high supplements of vitamin C have increased quantities of electron transport components and overall drug metabolism activities. Kinetic studies indicate no change in the apparent Km of N-demethylase, O-demethylase or hydroxylase for drug substrates in animals depleted or given high amounts of the vitamin. However, there are qualitative changes in both type I and II substrate-cytochrome P-450 binding. Ascorbic acid is not involved in microsomal lipid peroxidation or in any qualitative or quantitative change in phosphatidylcholine. Replenishing vitamin C-deficient animals with ascorbic acid required 3 to 7 days for the electron transport components and drug metabolism activities to return to normal levels. Induction with phenobarbital and 3-methylcholanthrene is not impaired in the deficient animal since drug metabolism activities are induced to the same extent as normal controls; however, the administration of delta-aminolevulinic acid, a precursor of heme synthesis, to deficient animals caused an increase in the quantity of cytochrome P-450. The effects of riboflavin deficiency on electron transport components and drug metabolism activities have been noted only in adult animals after prolonged periods of deficiency. Decreases in drug metabolism activities occur with both type I (aminopyrine and ethylmorphine) and type II (aniline) substrates. As was found with ascorbic acid deficiency, drug enzyme induction occurred to the same extent with phenobarbital in deficient and normal animals. In addition, it required from 10 to 15 days for the drug metabolism activities to return to normal levels when deficient animals were replenished with riboflavin. The effect of vitamin E on drug metabolism is specific in N-demethylase activities decrease while O-demethylase activities are not affected in the deficient state. This vitamin differs from ascorbic acid and riboflavin in that several laboratories have reported no quantitative decrease in cytochrome P-450, although there are some reports that it and delta-aminolevulinic acid dehydratase are lowered quantity of cytochrome in E-deficient animals. The effect of vitamin E, if any, on the P-450 is unresolved; an important question that requires further clarification. As with ascorbic acid there is no difference in the apparent Km of N-demethylase enzymes for varous substrates and the protective effect of vitamin E does not appear to be one of an antioxidant inhibiting microsomal lipid peroxidation.
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PMID:The effect of certain vitamin deficiencies on hepatic drug metabolism. 97 90