Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine.
A new, pharmacologically active metabolite of cocaine, ethylcocaine, has been reported in individuals after concurrent use of cocaine and ethanol. Formation of ethylcocaine may contribute to the common coabuse of these two drugs and the apparent danger of this practice. We have identified a nonspecific carboxyl-esterase that catalyzes the ethyl transesterification of cocaine to ethylcocaine in the presence of ethanol. In the absence of ethanol, this human liver esterase catalyzes the hydrolysis of cocaine to benzoylecgonine, a metabolite that is inactive as a psychomotor stimulant. A second human liver esterase is also described. This enzyme catalyzes hydrolysis of cocaine to ecgonine methyl ester, also inactive as a stimulant. These two liver esterases may play important roles in regulating the metabolic inactivation of cocaine.
Dean
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Department of Pathology, Indiana University School of Medicine, Indianapolis 46202-5122.
Christian
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D002265:Carboxylic Ester Hydrolases / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D003042:Cocaine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008099:Liver / Q000201:enzymology*; D015394:Molecular Structure; D008970:Molecular Weight
D000431:Ethanol; C005618:benzoylecgonine; D002265:Carboxylic Ester Hydrolases; C019921:cocaine esterase; C066444:cocaethylene; D003042:Cocaine