Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products.

Abstract

Trichloromethyl free radicals (. CCI) produced during a benzoyl peroxide decomposition of CCl4 covalently bind to hemin. Enzymatically produced . CCl3 by an NADPH anaerobic liver microsomal activation of CCl4, covalently binds to heme and heme degradation products from CO-binding particles. 14C from CCl4 covalently binds to heme and heme degradation products from liver CL-binding particles from rats treated with 14CCl4. In vivo covalent binding of 14CCl4 reactive metabolites to proteins from CO-binding particles is higher than that to the whole microsomal proteins. The possible correlation between binding of . CCl3 to heme and protein moieties of P-450 and CCl4 induced P-450 destruction is discussed.