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Related Experiment Videos

Ascorbic acid deficiency and hepatic UDP-glucuronyltransferase.

C M Neumann1, V G Zannoni

  • 1Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|July 1, 1988
PubMed
Summary

Dietary ascorbic acid (vitamin C) deficiency reduces specific hepatic microsomal UDP-glucuronyltransferase (UDPGT) activity for p-aminophenol in guinea pigs. This suggests vitamin C influences specific UDPGT isozymes, impacting drug metabolism.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Nutritional Science

Background:

  • Hepatic microsomal UDP-glucuronyltransferase (UDPGT) is crucial for detoxifying xenobiotics and endogenous compounds.
  • Ascorbic acid (vitamin C) plays a role in various metabolic processes, but its specific impact on UDPGT activity is not fully understood.
  • Previous studies indicated ascorbate deficiency affects hepatic cytochrome P-450 levels in guinea pigs.

Purpose of the Study:

  • To investigate the effect of dietary ascorbic acid on hepatic microsomal UDPGT activity towards specific substrates.
  • To determine if ascorbic acid influences specific UDPGT isozymes.
  • To explore the protective role of ascorbic acid against substrate-induced enzyme inhibition.

Main Methods:

  • Assessed UDPGT activity in liver microsomes from ascorbate-deficient and supplemented guinea pigs using p-aminophenol, bilirubin, and acetaminophen as substrates.

Related Experiment Videos

  • Investigated the impact of membrane-perturbing agents (sonication, Triton X-100) and cofactors (magnesium chloride) on enzyme activity.
  • Examined the in vitro protective effects of ascorbic acid, its analogs, and other antioxidants against substrate-induced enzyme inactivation.

    • Main Results:

    • Ascorbate deficiency led to a 33% reduction in UDPGT activity towards p-aminophenol, but not bilirubin or acetaminophen.
    • This reduction correlated with decreased hepatic microsomal cytochrome P-450 levels.
    • Ascorbic acid and glutathione protected UDPGT from substrate-induced inactivation in vitro, maintaining linear activity.
    • Membrane perturbation and magnesium chloride significantly altered UDPGT activity, with varying effects between the two dietary groups.

    Conclusions:

    • Dietary ascorbic acid specifically influences UDPGT isozymes involved in p-aminophenol conjugation.
    • The observed reduction in UDPGT activity in ascorbate deficiency may be linked to altered cytochrome P-450 levels and membrane properties.
    • Ascorbic acid and glutathione exhibit protective effects against UDPGT inactivation by excess substrate.