Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid variations on drug metabolism.
Pharmacogenomics investigates DNA and RNA variations in the human genome related to drug responses. Cytochrome P450 (CYP) is a supergene family of drug-metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical significance because it metabolizes approximately 20% of clinically administrated drugs and represents several variant alleles leading to adverse drug reactions or altering drug efficacy. Here, we review recent progress on understanding the interindividual variability of the CYP2C members and the functional and clinical impact on drug metabolism. We summarize current advances in the molecular modeling of CYP2C polymorphisms and discuss the structural bases and molecular mechanisms of amino acid variants of CYP2C members that affect drug metabolism.
Department of Biology and Chemistry, West University of Timisoara, 16 Pestalozzi, Timisoara 300115, Romania; Advanced Environmental Research Laboratories, West University of Timisoara, 4 Oituz, Timisoara 300086, Romania.
Adriana
A
Isvoran
Université Paris Diderot, Sorbonne Paris Cité, Inserm UMR-S 973, Molécules Thérapeutiques In silico, 39 rue Helene Brion, 75013 Paris, France; INSERM, U973, Paris, France.
Maxime
M
Louet
Department of Biology and Chemistry, West University of Timisoara, 16 Pestalozzi, Timisoara 300115, Romania; Advanced Environmental Research Laboratories, West University of Timisoara, 4 Oituz, Timisoara 300086, Romania.
Diana Larisa
DL
Vladoiu
Teacher Training Department, West University of Timisoara, Blvd. V. Parvan, Timisoara 300223, Romania.
Dana
D
Craciun
INSERM UMR_S1147, Centre Universitaire des Saints-Pères, 45 rue des saints-Pères, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Service de Biochimie, 20 rue Leblanc, 75015 Paris, France.
Marie-Anne
MA
Loriot
Université Paris Diderot, Sorbonne Paris Cité, Inserm UMR-S 973, Molécules Thérapeutiques In silico, 39 rue Helene Brion, 75013 Paris, France; INSERM, U973, Paris, France.
Bruno O
BO
Villoutreix
Université Paris Diderot, Sorbonne Paris Cité, Inserm UMR-S 973, Molécules Thérapeutiques In silico, 39 rue Helene Brion, 75013 Paris, France; INSERM, U973, Paris, France. Electronic address: maria.mitev@inserm.fr.
Maria A
MA
Miteva
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D000596:Amino Acids; D004364:Pharmaceutical Preparations; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System