P450 isoform CYP1A2 accounts for almost 95% of the primary
metabolism of caffeine. CYP1A2-catalyzed 3-demethylation
of caffeine results in the formation of 1,7-dimethylxanthine
(paraxanthine) (Figure 2). Paraxanthine may be demethylated
by CYP1A2 to form 1-methylxanthine, which may be oxidized
to 1-methyluric acid by xanthine oxidase. Paraxanthine may
also be hydroxylated by CYP2A6 to form 1,7-dimethyluric
acid, or acetylated by N-acetyltransferase 2 (NAT2) to form
5-acetylamino-6-formylamino-3-methyluracil, an unstable
compound that may be deformylated nonenzymatically to form
5-acetylamino-6-amino-3-methyluracil (Figure 2).8,9
Caffeine concentrations in coffee beverages can be quite variable.
A standard cup of coffee is often assumed to provide
100 mg of caffeine, but a recent analysis of 14 different specialty
coffees purchased at coffee shops in the US found that
the amount of caffeine in 8 oz (∼240 ml) of brewed coffee
ranged from 72–130 mg.10 Caffeine in espresso coffees ranged
from 58–76 mg in a single shot. Interestingly, the caffeine
content of the same type of coffee purchased from the same
store on six separate days varied from 130 to 282 mg per 8-oz
serving.