Metabolismus a káva

Genetic heterogeneity

• Interactions between coffee or caffeine intake and genetic polymorphisms
• Affecting the activity of phase I and phase II biotransformation enzymes [12]

CYP1A2

• A major role in caffeine metabolism
• Metabolic activation of potentially carcinogenic heterocyclic amines
• Two genetic polymorphisms alter the inducibility of CYP1A2
• In the 5'-flanking region of human CYP1A2 gene
• Functional significance of a C-› A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene

CYP1A2*1C

CYP1A2*1F

• Small case-control study of Japanese women
• Caffeine intake was not associated with recurrent pregnancy loss when CYP1A2 genotype was not considered
• In women who were homozygous for the CYP1A2*1F polymorphism
• Associated with high inducibility of CYP1A2
• Caffeine intake was positively associated with the risk of recurrent pregnancy loss [12]

CYP2A6

• Role in:
• Caffeine metabolism
• Nicotine metabolism
• Activation of procarcinogenic nitrosamines
• Number of distinct polymorphisms of CYP2A6 that affect its activity
• May affect smoking behavior and cancer risk
• Novel markers of susceptibility to carcinogens in diet [12]

NAT2 polymorphisms

• Affect its acetylation activity
• “slow acetylators”
• Essentially unable to acetylate the primary caffeine metabolite - paraxanthine [12]
• Aromatic amines in cigarette smoke and foods
• Are also acetylated by NAT2
• NAT2 polymorphisms
• Modulate the risk of several cancers in humans
• Bladder cnacer
• Colorectal cancer [12]

UGT genes polymorphisms

• Caffeic acid, a metabolite of chlorogenic acid
• Extensively glucuronidated through the activity of intestinal and hepatic UDP-glucuronosyltransferases (UGT)
• Genetic polymorphisms for 6 of the 16 human UGT genes
• Functional significance of polymorphism of UGT1A1 [12]

Peak plasma levels

• Within one hour after ingestion [1]

Nástup účinku

• Clinical effects within 15 min