Synthesis of cytochrome P-450 heme in ascorbic acid-deficient guinea pigs

Abstract

Studies were carried out in the guinea pig to compare the effects of ascorbic acid (AA) status on hepatic and blood hemoproteins and to evaluate the role of Δ-aminolevulinic acid (ALA) injections in the modulation of the adverse actions produced by AA depletion. Hepatic microsomal cytochrome P-450 concentration, drug metabolism and blood heme parameters are significantly (P < 0.05) lower in AA-deficient guinea pigs than in AA-adequate animals. Intraperitoneal injections of ALA were not effective in reversing hepatic cytochrome P-450 or blood heme parameters in AA- deficient guinea pigs. Urinary excretion of porphyrins and porphyrin precursors was lower or not changed in AA-depleted animals compared to AA-adequate guinea pigs. These studies support the hypothesis that AA deficiency does not block heme synthesis. However, the incorporation of [ 3H]ALA into hepatic cytochrome P-450 heme was less in AA-depleted animals than in AA-supplemented animals. This finding is consistent with a possible error in assembly of holoprotein from heme and apoprotein. Two additional findings were noted: (1) AA status had no significant effect on blood catalase activity, and (2) the anemia found in scorbutic guinea pigs was not associated with macrocytic changes.