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Query: UMLS:C0003969 (vitamin C deficiency)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vanadium has been reported to affect numerous physiological processes; however, a demonstration that vanadium deficiency consistently impairs biological function is lacking. The purpose of this study was to determine if the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, is affected by dietary supplementation of vanadate and/or chronic ascorbic acid deficiency. To determine if vanadium and/or ascorbic acid affected mineral metabolism, tissue minerals also were analyzed. Weanling male guinea pigs were assigned randomly to groups of 10 in a 2 x 2 factorial design. The dietary variables were ascorbate, 0.5 or 10 mg/day, and vanadium < 0.01 microgram or 0.5 microgram/g diet as NH4VO3 in a low Cr diet containing < 0.07 microgram Cr/g diet. After 21 weeks on this diet, guinea pigs receiving more ascorbate had lower liver weight/body weight ratios and increased bone copper. Testes weight/body weight ratios, hepatic glycogen and bone copper decreased while hepatic lipids, fecal bile acids, plasma cortisol and bone calcium and magnesium were increased by vanadium supplementation. An interaction between vanadium and ascorbate affected cholesterol excretion in feces, hepatic iron, plasma cholesterol concentration and the activity of HMG CoA reductase. This study provides evidence of increased bone mineral concentrations with vanadium supplementation and of an interaction between vanadium and ascorbate which affected cholesterol metabolism.
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PMID:Vanadium and ascorbate effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase, cholesterol and tissue minerals in guinea pigs fed low-chromium diets. 166 16

Guinea pigs fed a normal diet show the expected diurnal variation in 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Vitamin C deficiency, however, suppresses the diurnal peak activity of reductase, due to a decrease in active (unphosphorylated) enzyme. Inhibition of reductase is paralleled by both a fall in hepatic cholesterol synthesis and a rise in serum cholesterol. Incubation of normal guinea pig hepatic microsomes with physiologic and supraphysiologic concentrations of sodium ascorbate also leads to a concentration-dependent inhibition of reductase activity. Thus, dietary extremes of vitamin C may exert similar effects on reductase activity and cholesterolgenesis. Moreover, the changes in enzyme activity induced by ascorbic acid appear to be due in part to a direct effect of the vitamin on the microsomally bound enzyme.
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PMID:Ascorbic acid regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in guinea pig liver. 403 87

Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from d-glucuronate. The latter is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties with, and most likely identical to, UDP-glucuronosyltransferases. Non-glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others) stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their effect to increase vitamin C formation in vivo. Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily. l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene. Another fate of glucuronate is its conversion to d-xylulose in a five-step pathway, the pentose pathway, involving identified oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Transmembrane electron transfer systems using ascorbate or NADH as electron donors serve to reduce semidehydroascorbate present in neuroendocrine secretory vesicles and in the extracellular medium. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH. The degradation of vitamin C in mammals is initiated by the hydrolysis of dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to oxalate, CO(2) and l-erythrulose. This is at variance with bacteria such as Escherichia coli, which have enzymatic degradation pathways for ascorbate and probably also dehydroascorbate.
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PMID:Vitamin C. Biosynthesis, recycling and degradation in mammals. 1722 74

Hyperhomocysteinemia was first associated with degenerative disease by observation of accelerated arteriosclerosis in children with inherited disorders of cystathionine synthase, methionine synthase, and methylene tetrohydrofolate reductase. The metabolic blockade of sulfate synthesis from homocysteine thiolactone in malignant cells is ascribed to a deficiency of a chemopreventive derivative of homocysteine thiolactone that occurs in normal cells. Its chemical structure was elucidated by the organic synthesis of thioretinamide from retinoic acid and homocysteine thiolactone. Oxidation of the sulfur atom of homocysteine is inhibited in scorbutic guinea pigs, demonstrating ascorbate function in sulfate synthesis from homocysteine. Studies of homocysteine metabolism in protein energy malnutrition led to the conclusion that the biosynthesis of thioretinamide from the retinol of transthyretin is catalyzed by dehydroascorbate and superoxide generated from the heme oxygenase group of cystathionine synthase. Newly synthesized thioretinamide is complexed with cobalamin to form thioretinaco, which is activated by ozone and oxygen to function as the active site of oxidative phosphorylation. In accordance with the trophoblastic theory of cancer, pancreatic enzymes are believed to be oncolytic because they hydrolyze the homocysteinylated proteins, nucleic acids and glycosaminoglycans of malignant tissues. The clonal selection of malignant cells that are deficient in the heme oxygenase function of cystathionine synthase produces cells dependent upon glycolysis for ATP synthesis, since they are deficient in synthesis of thioretinamide, thioretinaco and thioretinaco ozonide. The vulnerable plaque of arteriosclerosis originates from complexes of microbes with homocysteinylated lipoproteins, obstructing vasa vasorum narrowed by endothelial dysfunction, causing arterial ischemia, and intimal micro-abscesses. Degenerative diseases may be ameliorated by a proposed therapeutic protocol of thioretinamide with pancreatic enzymes.
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PMID:Chemical pathology of homocysteine. V. Thioretinamide, thioretinaco, and cystathionine synthase function in degenerative diseases. 2216 99