Cytochrome P-450 inactivation: structure of the prosthetic heme adduct with propyne.

Abstract:

:Hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats is destroyed by propyne in a reduced nicotinamide adenine dinucleotide dependent process which also results in vivo in the accumulation of an abnormal green porphyrin. The green porphyrin has been identified by its electronic absorption, mass spectrometric, and nuclear magnetic resonance properties as the isomer of N-(2-oxopropyl)protoporphyrin IX in which the alkylated nitrogen is that of pyrrole ring A. Alkylation of the other nitrogens in the parent heme is quantitatively unimportant, although evidence for traces of the resulting adducts has been obtained. The green porphyrin exhibits a circular dichroism spectrum and is therefore the result of a chirally selective or specific interaction. The structure of the green porphyrin implicates a cytochrome P-450 destructive mechanism in which a species formed by catalytic oxidation of the acetylenic moiety reacts with the nitrogens of prosthetic heme. The possible nature of the reactive intermediate is discussed.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Ortiz de Montellano PR,Kunze KL

doi

10.1021/bi00528a033

subject

Has Abstract

pub_date

1981-12-08 00:00:00

pages

7266-71

issue

25

eissn

0006-2960

issn

1520-4995

journal_volume

20

pub_type

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