TY - JOUR
T1 - Cytochrome P450 and the biological clock in mammals
AU - Froy, Oren
PY - 2009
Y1 - 2009
N2 - Cytochrome P450 (CYP) is a diverse superfamily of hemoproteins found in a large number of organisms. Most cytochrome P450 enzymes have monooxygenase activity and are involved in detoxification and hormone and lipid metabolism. In drug metabolism, the chemical modification or degradation of chemicals including exogenous and endogenous compounds, cytochrome P450 is probably the most important element of oxidative metabolism. The present understanding of the mechanisms of induction of cytochrome P450 enzymes and their regulation has made considerable progress during the last few years. However, it remains the subject of intense scientific research to better understand how the expression of cytochrome P450 enzymes is regulated at the molecular level. It has been known for three decades that the expression of cytochrome P450 gene family members is regulated by the biological clock. In addition, hepatic P450 monooxygenases metabolize melatonin, the pineal hormone whose expression is controlled by the biological clock and, in turn, resets the biological clock. This review will summarize our present understanding on how the biological clock regulates the expression and activity of cytochrome P450 enzymes to affect pharmacokinetics and detoxification and hormone and lipid metabolism and how melatonin metabolism and cytochrome P450 enzyme activity can affect circadian rhythms in mammals.
AB - Cytochrome P450 (CYP) is a diverse superfamily of hemoproteins found in a large number of organisms. Most cytochrome P450 enzymes have monooxygenase activity and are involved in detoxification and hormone and lipid metabolism. In drug metabolism, the chemical modification or degradation of chemicals including exogenous and endogenous compounds, cytochrome P450 is probably the most important element of oxidative metabolism. The present understanding of the mechanisms of induction of cytochrome P450 enzymes and their regulation has made considerable progress during the last few years. However, it remains the subject of intense scientific research to better understand how the expression of cytochrome P450 enzymes is regulated at the molecular level. It has been known for three decades that the expression of cytochrome P450 gene family members is regulated by the biological clock. In addition, hepatic P450 monooxygenases metabolize melatonin, the pineal hormone whose expression is controlled by the biological clock and, in turn, resets the biological clock. This review will summarize our present understanding on how the biological clock regulates the expression and activity of cytochrome P450 enzymes to affect pharmacokinetics and detoxification and hormone and lipid metabolism and how melatonin metabolism and cytochrome P450 enzyme activity can affect circadian rhythms in mammals.
KW - Biological clock
KW - Circadian rhythms
KW - Cytochrome P450
KW - DBP
KW - Melatonin
KW - PPAR
KW - Pharmacokinetics
KW - ROR
UR - http://www.scopus.com/inward/record.url?scp=65549100013&partnerID=8YFLogxK
U2 - 10.2174/138920009787522179
DO - 10.2174/138920009787522179
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C2 - 19275546
AN - SCOPUS:65549100013
SN - 1389-2002
VL - 10
SP - 104
EP - 115
JO - Current Drug Metabolism
JF - Current Drug Metabolism
IS - 2
ER -