Disease relevance of CYP7

• These studies demonstrate 1) premature weaning on day 2 does not prevent neonatal hypercholesterolemia on day 5, 2) premature weaning causes a decrease in hepatic cholesterol 7 alpha-hydroxylase activity that persists into adult life, and 3) dietary cholesterol intake in early life is unable to negate premature weaning-induced changes [1].

High impact information on CYP7

• Early weaning did not influence the fecal excretion of steroids or cholesterol 7 alpha-hydroxylase activity but resulted in a slight decrease in the hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity when they were challenged with a high cholesterol diet [2].
• Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7 alpha-hydroxylase activity [3].
• Taurocholic acid had no direct effect on cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes as assessed by addition of the bile acid to the assay mixture [3].
• Since 7 alpha-hydroxy-3-oxo-4-cholestenoic acid is believed to be an important precursor of chenodeoxycholic acid, this study shows that the first reactions in the biosynthesis of bile acids can be exclusively mitochondrial and thereby bypass microsomal cholesterol 7 alpha-hydroxylase as the rate-limiting enzyme [4].
• 7alpha-hydroxylase activity toward both isomers of 24-hydroxycholesterol [(24S) and (24R)] was found in a partially purified and reconstituted cholesterol 7alpha-hydroxylase (CYP7A) enzyme fraction from pig liver microsomes [5].

Biological context of CYP7

• We conclude that TaqI RFLP analysis of the CYP7 gene is a reliable indicator for TC in these swine [6].
• PSY intake with HF resulted in up-regulation of C7H and HMG-CoA reductase activities (P < 0.05) [7].
• Cholesterol feeding induced cyp7 mRNA levels but suppressed isbt gene expression [8].
• Hepatic cholesterol 7alpha-hydroxylase (CYP7A) and sterol 27 hydroxylase activities were measured in fetal, newborn, suckling, and weaned piglets from 76 d into gestation to 49 d of age [9].

Anatomical context of CYP7

• Effects of carbon monoxide, nitrogen, ferricytochrome c and p-hydroxymercuribenzoate were studied on cholesterol 7 alpha-hydroxylase activity of swine hepatic microsomes [10].
• Despite reductions in rat bile flow there were no alterations in liver morphology, liver plasma membrane Na-K-ATPase activity, microsomal cholesterol-7 alpha-hydroxylase activity or low-dose indocyanine green clearance during the period of observation [11].

Associations of CYP7 with chemical compounds

• The inhibitory action was exerted specifically on activity of cholesterol 7 alpha-hydroxylase because conversion of [14C] 7 alpha-hydroxycholesterol to bile acids by pig hepatocytes was not affected [3].
• In contrast, HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase were not affected by the drug [12].
• 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A) [5].
• Cholesterol 7alpha-hydroxylase activity was assayed in liver microsomes from guinea pigs supplemented with ascorbate and from guinea pigs in a state of ascorbate deficiency [13].
• This marked lack of mitochondrial specificity towards the steroid side chains is in direct contrast with the rat liver microsomal cholesterol 7alpha-hydroxylase, which has a high specificity for the side chain [14].

Other interactions of CYP7

• The activities of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, acetyl-CoA carboxylase (ACX), fatty acid synthetase (FAS) and other lipogenic enzymes in several tissues were determined [15].
• CONCLUSIONS: A low dose of the ASBT inhibitor, SC-435, significantly reduces plasma LDL cholesterol through enhanced LDL receptor-mediated LDL apoB clearance, secondary to increased expression of cholesterol 7alpha-hydroxylase [16].

Analytical, diagnostic and therapeutic context of CYP7

• Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations [17].

References