Species-Specific and Age-Dependent Bile Acid Composition: Aspects on CYP8B and CYP4A Subfamilies in Bile Acid Biosynthesis

Abstract

The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12alpha or 6alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.

Interaction between Alcohol Consumption and CYP 2C19 Gene Polymorphism in Relation to Oesophageal Squamous Cell Carcinoma

“…Current researches suggested that some CYP isoforms, such as CYP1A [8], CYP2B [9], CYP2C [10], CYP2D [11], participate arachidonic acid metabolism. CYP2C19, one human cytochrome P450 enzyme, is not only a clinically important metabolic enzyme responsible for the metabolism of a number of therapeutic drugs but also the key enzyme of EETs synthesis and abundantly expressed in endothelial and smooth muscle cells [12], [13] Recently, there were several studies concerning the CYP2C19 polymorphism and cancer susceptibility [14]–[17].…”

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

“…Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) (Node et al, 2001;Fichtlscherer et al, 2004;Lundell and Wikvall, 2008;Fava et al, 2008). CYP2C19 is one of the human cytochrome P450 enzymes, and it is abundantly expressed in endothelial and smooth muscle cells (Imig et al, 2000;Ercan et al, 2008).…”

Bile acids as regulatory molecules

“…The gene encoding CYP8B1 is also highly regulated at the transcriptional level by many of the same mechanisms regulating CYP7A1. However, there some differences in the regulation of the genes encoding CYP7A1 and CYP8B1 ( 29 ). The enzymes in the bile acid biosynthetic pathway are located at many different cellular locations in the hepatocyte, including smooth endoplasmic reticulum, mitochondria, peroxisomes, and cytoplasm.…”