Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain

doi:10.1016/0006-2952(93)90139-N

Biochemical Pharmacology

Volume 45, Issue 3, 9 February 1993, Pages 647-658

https://doi.org/10.1016/0006-2952(93)90139-N Get rights and content

Abstract

We studied the subcellular distribution of cytochrome P450 and related monooxygenase activities in six regions of human brains removed at autopsy. The content of total cytochrome P450 was found to be at least nine times higher in the mitochondrial fraction than in the microsomes in all the regions studied. However, cytochrome P450-dependent enzymatic activities which are representative of different isoforms metabolizing exogenous molecules exhibited a microsomal prevalence, a situation previously observed in rat brain. The other drug-metabolizing enzymes catalysing functionalization and conjugation reactions, presented the following characteristics in human brain: (i) a low activity of NADPH-cytochrome P450 reductase, which also catalyses the reduction of some xenobiotics; (ii) a high specific activity of the membrane-bound epoxide hydrolase; (iii) among the enzymes catalysing conjugation reactions, 1-naphthol-UDP-glucuronosyltransferase activity was barely or not detectable, whereas the mean glutathione-S-transferase activity was 15 times higher than the activity measured in rat brain. The presence of several drug-metabolizing enzyme activities in human brain microvessels, and particularly the high activity of epoxide hydrolase, suggests a participation of these enzymes in the metabolic blood-brain barrier.

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Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain

Abstract

Biochem Pharmacol

Neurochem Int

Brain Res Rev

Life Sci

Trends Neurosci

J Neurosci Methods

J Neurosci Methods

Biochem Pharmacol

Clin Chem

Anal Biochem

Mol Pharmacol

Brain Res

Biochem Pharmacol

J Pharmacol Exp Ther

J Neuroendocrinol

J Biol Chem

Biochem Biophys Res Commun

Mol Pharmacol

Arch Biochem Biophys

Human Exp Toxicol

Drug Metabolism: Chemical and Biochemical Aspects