The interaction of human and bovine serum proteins with CYP3A in human liver microsomes: inhibition of testosterone 6beta-hydroxylation by albumin, alpha-globulins, alpha(1)-acid glycoprotein and gamma-globulins

• Published in: Toxicology letters Vol. 136; no. 1; pp. 33 - 41
• Main Authors: Matsumoto, Satoshi, Ding, Li R, Ishii, Mikio, Fischer, Nancy E, Inaba, Tadanobu
• Format: Journal Article
• Language: English
• Published: Netherlands 15.11.2002
• Subjects: Alpha-Globulins - pharmacology; Animals; Aryl Hydrocarbon Hydroxylases - metabolism; Blood Proteins - pharmacology; Cattle; Chromatography, Thin Layer; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; gamma-Globulins - pharmacology; Glycated Hemoglobin A - pharmacology; Humans; Indicators and Reagents; Kinetics; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Oxidoreductases, N-Demethylating - metabolism; Protein Binding; Serum Albumin - pharmacology; Serum Albumin, Bovine - pharmacology; Steroid Hydroxylases - antagonists & inhibitors; Steroid Hydroxylases - metabolism

The effects of human and bovine serum proteins on CYP3A activity, using testosterone as the probe substrate, were investigated in human liver microsomes. Serum albumin, alpha-globulins, and alpha(1)-acid glycoprotein (alpha(1)-AGP) of both species significantly inhibited testosterone 6beta-hydroxyla...