Effect of superoxide generation and dismutation on hydroxylation reactions catalyzed by liver microsomal cytochrome P-450.

Abstract The mechanism of hydroxylation reactions catalyzed by an enzyme system containing cytochrome P-450 was investigated with the aid of highly purified enzymes known to catalyze the generation and decomposition of superoxide (O2·-). The liver microsomal enzyme system used in these studies was previously solubilized and resolved into three components (cytochrome P-450, TPNH-cytochrome P-450 reductase, and phosphatidylcholine) which are required for the hydroxylation of a variety of fatty acids, hydrocarbons, and drugs. Superoxide dismutase (erythrocuprein) was shown to inhibit benzphetamine hydroxylation in the presence of TPNH, molecular oxygen, and the reconstituted liver microsomal enzyme system. The extent of inhibition was the same determined by benzphetamine-dependent TPNH oxidation and by benzphetamine demethylation, which results from hydroxylation of the N-methyl group and the subsequent liberation of formaldehyde. The dismutase caused complete inhibition only in the presence of a concentration of salt which itself was partially inhibitory. A superoxide generating system (xanthine and xanthine oxidase) was shown to couple with cytochrome P-450 to support the hydroxylation of benzphetamine and ethylmorphine in the absence of TPNH and the reductase. The coupling was dependent upon the presence of phosphatidylcholine and was abolished by the addition of the dismutase.

• Publication year

  1971

• Venue

  Journal of Biological Chemistry

• Publication date

  1971-12-25

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(19)45853-5PMID 4400080
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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