Ascorbic acid deficiency decreases the expression of CYP4A1 in liver microsomes of guinea pigs.

Res Commun Mol Pathol Pharmacol 1997 Jan;95(1):3-10    

Roomi MW; Ogg M; Tsao CS; Gibson GG
Linus Pauling Institute of Science and Medicine, Palo Alto, CA, USA.

The cytochrome P - 450 monooxygenase system plays a central role in the oxidation of a wide variety of structurally unrelated compounds. Its contribution is affected by nutritional and several other factors. Ascorbic acid (AA) deficiency decreases the content of cytochrome P - 450 in liver microsomes of guinea pigs (GPs). Included in the group of cytochromes P - 450 are the phenobarbital and 3-methylcholanthrene inducible moieties. In the present study the effect of AA status on another specific cytochrome P - 450 , CYP4A1 , laurate omega-hydroxylase was investigated. Ascorbic acid may selectively increase or decrease certain forms of cytochromes. For four weeks adult male Hartley GPs were fed a diet containing 2.5 (Group I), 0.1 (Group II) and 0% (Group III) AA. The liver microsomes were isolated at this stage and cytochrome P - 450 content was determined. Group III showed a significant decrease in cytochrome P - 450 compared to groups I and II. They also showed a marked decrease in aminopyrine N-demethylase activity. The expression of CYP4A1 was evaluated using Western blot and anti- CYP4A1 antibody. Group III GPs showed a marked decrease in CYP4A1 expression . Groups I and II showed similar expression . This study demonstrates that CYP4A1 , a specific cytochrome induced by hypolipidemic agents, is decreased by AA deficiency