Biomaterial Database

Self-catalyzed destruction of cytochrome P-450: covalent binding of ethynyl sterols to prosthetic heme. 1979

P R Ortiz de Montellano, and K L Kunze, and G S Yost, and B A Mico

The hepatic pigment accumulated as a consequence of the self-catalyzed destruction of cytochrome P-450 by norethisterone (17-hydroxy-19-nor-17 alpha-pregn-4-en-20-yn-3-one), after acidic methylation and purification, consists of two virtually identical, probably isomeric, porphyrins. Radiolabeled norethisterone is incorporated into both porphyrin products. The major of the two porphyrins exhibits a mass spectrometric molecular ion exactly equivalent to the sum of norethisterone and dimethylprotoporphyrin IX, less two hydrogen atoms: unequivocably demonstrating covalent association of the sterol with this porphyrin in a 1:1 ratio. Cytochrome P-450 is therefore destroyed by self-catalyzed addition of norethisterone to its heme prosthetic group. Cytochrome P-450 is also destroyed by norgestrel (13-ethyl-17-hydroxyl-18, 19-dinor-17 alpha-pregn-4-en-20-yn-3-one) and by 1-ethynylcyclohexanol but not by 17-hydroxy-19-nor-17alpha-pregn-4,20-dien-3-one. The destructive potential is thus clearly a property of the propargylic alcohol function. A mechanism involving enzymatic oxidation of the triple bond is postulated.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009640	Norethindrone	A synthetic progestational hormone with actions similar to those of PROGESTERONE but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for CONTRACEPTION.	19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17alpha)-,Ethinylnortestosterone,Norethisterone,Norpregneninolone,Conceplan,Micronor,Monogest,Nor-QD,Norcolut,Norcolute,Norethindrone, (1 beta)-Isomer,Norlutin,Nor QD,NorQD
D010860	Pigments, Biological	Any normal or abnormal coloring matter in PLANTS; ANIMALS or micro-organisms.	Biological Pigments
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus