Biomaterial Database

Ascorbic acid and cytochrome P-450. 1978

L E Rikans, and C R Smith, and V G Zannoni

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D003580	Cytochromes	Hemeproteins whose characteristic mode of action involves transfer of reducing equivalents which are associated with a reversible change in oxidation state of the prosthetic group. Formally, this redox change involves a single-electron, reversible equilibrium between the Fe(II) and Fe(III) states of the central iron atom (From Enzyme Nomenclature, 1992, p539). The various cytochrome subclasses are organized by the type of HEME and by the wavelength range of their reduced alpha-absorption bands.	Cytochrome
D004591	Electrophoresis, Polyacrylamide Gel	Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.	Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX