Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking.
It has been realized recently that the primary metabolism of caffeine in humans is catalyzed by P-450IA2 and that the rate of caffeine metabolism can be estimated from a metabolic ratio in a single urine sample. A population of 178 students including 19 smokers were subjected to this caffeine test to establish their P-450IA2 index. Both stated numbers of cigarettes smoked per day and urinary cotinine levels as a confirmatory measure correlated significantly with enzyme activity showing dose-effect relationships (r = 0.62 and 0.89, respectively). Nevertheless, more nonsmokers than smokers had the highest enzyme indexes, suggesting that dietary elements or other factors may determine P-450IA2 activities in populations. Because P-450IA2 is a monooxygenase that may be confined to the liver, caffeine reveals directly the Ah-receptor-dependent enzyme induction only in the liver, but it may also be a signal of induction elsewhere.
Kalow
W
W
Department of Pharmacology, University of Toronto, Ontario, Canada.
Tang
B K
BK
D002110:Caffeine; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D006801:Humans; D008099:Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis*; D010947:Plants, Toxic; D012907:Smoking / Q000378:metabolism*; D014026:Nicotiana; D014527:Uric Acid / Q000032:analysis; D014970:Xanthines / Q000032:analysis
D014970:Xanthines; D014527:Uric Acid; D002110:Caffeine; C053085:1-methylxanthine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2