Cytochrome P450 Isoforms and the Metabolism of Volatile Hydrocarbons of Low Relative Molecular Mass

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Cytochrome P450 Isoforms and the Metabolism of Volatile Hydrocarbons of Low Relative Molecular Mass: Tamie NAKAJIMA. Department of Hygiene, Shinshu University School of Medicine—Cytochrome P450 isoforms responsible for the metabolism of volatile hydrocarbons of low relative molecular mass are reviewed. Rat CYP2E1 catalyse the metabolism of all hydrocarbons with a low Km, whereas CYP1A1/2, CYP2B1/2 and CYP2C11/6 catalyse the metabolism of many hydrocarbons with a high Km although the contribution of the first two is minimal. The metabolism of hydrocarbons is affected by physiological and environmental factors, changes in the expression of P450 isoforms and the affinity of the chemicals for the isoforms. Human CYP2E1 also catalysed all of the hydrocarbons investigated, with the same kinetics as that of rat CYP2E1. Human CYP2B6 and CYP2C8 catalyse the metabolism of some hydrocarbons, but with slighty different catalytic properties for the formation of o- and p- cresol from toluene. Although CYP2B1/2 is poorly expressed in liver microsomes from control rats, CYP2B6 is found immunochemically to be constitutive in human liver microsomes. Human CYP1A2 also catalyses the metabolism of some organic solvents, with varying kinetic and catalytic features. The contribution of human CYP3A3, CYP3A4 and CYP3A5 to metabolism is very low. In conclusion, CYP2E1 is an essential isoform for the metabolism of hydrocarbons in both rodents and humans, especially at low concentrations. (J Occup Health 1997; 39: 83-91)