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Ascorbic acid and cytochrome P-450.

L E Rikans, C R Smith, V G Zannoni

    The Journal of Pharmacology and Experimental Therapeutics
    |March 1, 1978
    PubMed
    Summary
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    Ascorbic acid deficiency reduces liver cytochrome P-450 in guinea pigs by affecting the protein part, not heme synthesis. This impacts drug metabolism and detoxification pathways.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Nutritional Science

    Background:

    • Liver microsomal cytochrome P-450 is crucial for metabolizing xenobiotics.
    • Ascorbic acid (vitamin C) is essential for various physiological processes, including those in the liver.
    • Previous studies indicate a reduction in cytochrome P-450 activity in ascorbic acid-deficient animals.

    Purpose of the Study:

    • To investigate the biochemical basis for the reduction of liver microsomal cytochrome P-450 in ascorbic acid-deficient guinea pigs.
    • To determine if heme synthesis or the apoprotein moiety of cytochrome P-450 is affected by ascorbic acid deficiency.

    Main Methods:

    • Assessed activities of key heme synthesis enzymes (ALA synthetase, ALA dehydratase, ferrochelatase).
    • Quantified mitochondrial heme levels.

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  • Analyzed microsomal polypeptide profiles using SDS-PAGE and heme staining.
  • Conducted enzyme induction studies with specific compounds.

    • Main Results:

    • Heme synthesis enzyme activities and mitochondrial heme levels were not significantly altered by ascorbic acid deficiency.
    • Ascorbic acid deficiency impaired the induction of ALA synthetase.
    • SDS-PAGE revealed quantitative differences in specific cytochrome P-450 polypeptide bands between normal and deficient microsomes.
    • Deficient microsomes showed reduced levels of 44,000, 52,000, and 57,000 Da polypeptides and increased levels of 54,000 and 55,000 Da polypeptides.

    Conclusions:

    • Ascorbic acid deficiency does not impair heme availability for cytochrome P-450 synthesis.
    • The deficiency appears to affect the apoprotein component of cytochrome P-450, leading to altered expression of specific isoforms.
    • These alterations in cytochrome P-450 may have significant implications for drug metabolism and detoxification in ascorbic acid-deficient states.