Biomaterial Database

Metabolism of dihalomethanes to carbon monoxide. II. In vitro studies. 1975

V L Kubic, and M W Anders

Dibromomethane was metabolized to carbon monoxide and inorganic bromide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen. This biotransformation was characterized with respect to time course, microsomal protein concentration, pH, and temperature. The metabolism of dihalomethanes to carbon monoxide followed the halide order; thus, diiodomethane yielded the greatest amount of carbon monoxide, whereas dichloromethane yielded the smallest amount. A KM of approximately 16 mM was established for dibromomethane while the Vmax was found to be about 8 nmol of CO per mg of microsomal protein per min. Cytochrome P-450 was found to bind dibromomethane to produce a type I binding spectrum. Pretreatment with phenobarbital increased both microsomal cytochrome P-450 levels and the rate of conversion of dibromomethane to carbon monoxide. Pretreatment with cobaltous chloride or storage of microsomal preparations at 4 degrees C resulted in parallel reductions of both cytochrome P-450 levels and the rate of formation of carbon monoxide from dibromomethane. SKF 525-A, ethylmorphine, and hexobarbital inhibited the conversion of dibromomethane to carbon monoxide. Microsomal preparations from rat lung metabolized this substrate at about 18% of the rate found in liver microsomes. The requirement for both NADPH and molecular oxygen, the inhibitory effects of SKF 525-A, ethylmorphine, and hexobarbital on the production of carbon monoxide from dibromomethane, and the correlation established between microsomal cytochrome P-450 levels and the rate of metabolism of dihalomethanes to carbon monoxide after treatments that alter the cytochrome to P-450 content suggest that these compounds are metabolized to carbon monoxide via a cytochrome P-450-dependent system.

UI	MeSH Term	Description	Entries
D008697	Methane	The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed)
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
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
D009022	Morphine Derivatives	Analogs or derivatives of morphine.	Morphines
D009928	Organ Specificity	Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.	Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011335	Proadifen	An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.	Propyladiphenin,Diethylaminoethyldiphenylpropyl Acetate,Proadifen Hydrochloride,SK&F-525-A,SK-525A,SKF-525-A,SKF-525A,Acetate, Diethylaminoethyldiphenylpropyl,Hydrochloride, Proadifen,SK 525A,SK&F 525 A,SK&F525A,SK525A,SKF 525 A,SKF525A
D002248	Carbon Monoxide	Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)	Monoxide, Carbon
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
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme