Prostanoids catabolism

While microsomal co-hydroxylation is not believed to represent a major pathway for hepatic fatty acid catabolism under normal physiological conditions, this highly inducible pathway may become important under certain conditions such as fasting or exposure to peroxisome proliferators. In addition to FA catabolism, the cytochrome P450 4As (CYP4As) involved in this pathway catabolize leukotrienes and prostanoids and also generate bioactive molecules from arachidonic acid co-hydroxylation. 

Prior to the demonstration of AA metabolism by P450, several groups demonstrated the role of microsomal P450s in the o>/a)-l hydroxylation of prostanoids "- and, more recently, leukotrienes- . Most of these reactions are considered to be involved in eicosanoid catabolism and excretion, but their potential relevance in eicosanoid bioactivation or inactivation, and/or in the control of organ/cell eicosanoid levels has only begun to be explored. We will first discuss the role of P450 in the metabolism of eicosanoids, and then concentrate on the studies of its role in AA metabolism and bioactivation. 

Many studies indicate an association between high blood pressure in experimental animals and abnormalities in urinary prostanoid excretion, a presumed index of the balance between renal prostanoid production and catabolism in vivo, and in rates of prostanoid synthesis and catabolism by renal structures and subcellular fractions in vitro. The urinary excretion of PGE2 is unchanged or decreased in spontaneously hypertensive rats, decreased in genetically hypertensive mice, in female genetically hypertensive rats (New Zealand strain) and in hypertensive Dahl salt-sensitive rats and either unchanged" or increased" in rats with two kidney-one clip... 

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