PHARMACOLOGY

 CYP 1A::

Two major isoforms are grouped in family 1A Ironically 1A1 was one of the first identified yet its presence in liver tissue is questionable It occurs primarily in extrahepatic tissue such as placenta 

1A2 is a major isoform that is inducible by tobacco smoking Phenacetin O-dealkylation caffeine 3 -demethylation and theophylline 8-hydroxylation are some of the reactions catalyzed by CYP 1A2 

The 1A2 isoform is one of the law expressed consistently across animal models Animal data thus translate into human experience quite well 

CYP 2A6 and 2B6 ::

Each of these isoforms is under study at this time Using compounds called probe drugs scientists are elucidating the properties of these enzymes in people Probes are drugs that are metabolized solely and specifically by the enzyme system under study By establishing a clear baseline using the probe changes in metabolism can be measured by introducing inhibitors inducers and other substrates into the system 

        Coumarin 7-hydroxylation has proven relatively specific for 2A6 while 2B6 is induced by phenobarbital and other antiepileptic drugs 

    The 2B6 isoform is responsible for increased clearance of several drugs after phenobarbital -type induction in people .2A6 catalyzes the oxidative metabolism of coumarin derivatives including psoralens and aflatoxin B1

CYP 2C ::

The 2C system has been well studied in rat models but the differences between rodent and human enzymes are marked for these isoenzymes 2C8-10 are the best known human variants and they metabolize mephenytoin phenytoin and tolbutamide However actions have not been attributed to specific isoforms and gender differences further complicate research into the 2C family 

CYP 2E1 ::

The 2E1 system is also in need for specific study particularly because it is important in hepatotoxicity and careinogenesis caused by chemicals such as benzene and nitrosamines The isoform responsible for metabolism of more than 60 known substance can be affected by alcohol consumption drugs such as isoniazid and conditions such as diabetes ketonemia and obesity Among the few known probes for 2E1 are the carcinogens dimethylnitrosamine and p-nitrophenol which are of course of no use in human research