Disease relevance of C03594

• Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage [1].
• Serum 7 alpha-hydroxycholesterol as a new parameter of liver function in patients with chronic liver diseases [2].
• The serum 7 alpha-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 +/- 59 pmol/mL vs. 237 +/- 97 pmol/mL; mean +/- SD) [2].
• Four bile fistula patients were administered consecutively two or more of the following 3H-labeled bile acid intermediates: 7 alpha-hydroxycholesterol, 7 alpha-hydroxy-4-cholesten-3-one, 5 beta-cholestane 3 alpha,7 alpha,26-triol, 26-hydroxycholesterol,7 alpha,26-dihydroxy-4-cholesten-3-one, and 5-cholestene-3 beta,12 alpha-diol [3].
• The serum levels of esterified and free 7 alpha-hydroxycholesterol in patients with cholelithiasis were 198.0 +/- 90.3 and 48.3 +/- 19.8 pmol/ml (mean +/- SD), respectively, and were similar to those in patients without hepatobiliary diseases [4].

High impact information on C03594

• Increased serum 7 alpha-hydroxycholesterol is probably indicative of an accelerated bile acid synthesis rate due to increased activity of cholesterol 7 alpha-hydroxylase, the enzyme catalyzing the first step in the major pathway of bile acid synthesis [5].
• The serum 7 alpha-hydroxycholesterol level (nanomoles per liter) was significantly increased in BRIC patients: 326 +/- 179 versus 171 +/- 90 in controls [5].
• Serum 7 alpha-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range [2].
• Serum 7 alpha-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities [2].
• 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 [6].

Chemical compound and disease context of C03594

• Accumulation of 7 alpha-hydroxycholesterol in liver tissue of patients with cholesterol gallstones [7].

Biological context of C03594

• Cholesterol and bile acid synthesis in Hep G2 cells. Metabolic effects of 26- and 7 alpha-hydroxycholesterol [8].
• We found that concentrations of 7 alpha-hydroxycholesterol obtained after alkaline hydrolysis were higher than those without alkaline hydrolysis, indicating that a considerable amount of 7 alpha-hydroxycholesterol in human serum is present in esterified form [4].
• Transfection of COS-cells with a cDNA coding for human cholesterol 7 alpha-hydroxylase resulted in significant production of cholesterol 7 alpha-hydroxylase enzyme and intracellular accumulation of the product, 7 alpha-hydroxycholesterol [9].
• Sex difference in serum 7 alpha-hydroxycholesterol levels in the rat reflect hepatic activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase and cholesterol 7 alpha-hydroxylase [10].
• After adjusting for current size, birthweight and gestational age were significantly related to plasma lathosterol and 7-alpha hydroxycholesterol [11].

Anatomical context of C03594

• The findings of the present report indicate that the human liver cell has the capacity to synthesize both primary bile acids via multiple routes from cholesterol and 7 alpha-hydroxycholesterol [12].
• 25-Hydroxycholesterol, 20 alpha-hydroxycholesterol, 7 alpha-hydroxycholesterol, and 5 alpha-hydroxy-6-ketocholestanol, when added to cultures of human lymphocytes in lipoprotein-depleted medium (LPDM) at a concentration of 2.5 x 10(-6) M, inhibit E-rosette formation with sheep red blood cells [13].
• Formation of 7 alpha-hydroxycholesterol by rat liver microsomes was quantitated using a gas chromatograph-mass spectrometer operated in selected ion monitoring mode [14].
• Microsomes from normal rat livers incubated for different periods were found to yield increased 7 alpha-hydroxycholesterol with time [14].
• The insertion of 7 alpha-hydroxycholesterol into erythrocyte membranes resulted in an increase in protein helical structure which was comparable to that observed for erythrocyte membranes enriched with pure cholesterol by 50% [15].

Associations of C03594 with other chemical compounds

• Analysis of free and esterified sterols from mice fed a cholesterol-free diet resulted in the identification and quantitation of six regulatory oxysterols: 24-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, and 7-ketocholesterol [16].
• The second metabolite was facilely produced when endogenous 7 alpha-hydroxycholesterol was incubated with hamster liver microsomes and NADPH, but not with rat liver microsomes [17].
• Endogenous 7-oxocholesterol is an enzymatic product: characterization of 7 alpha-hydroxycholesterol dehydrogenase activity of hamster liver microsomes [18].
• Bile acid synthesis in isolated rat liver cells. The effect of 7 alpha-hydroxycholesterol [19].
• Similarly, Triton X-100, Renex-30, Kyro EOB, Cutscum, and Emulgen 911 all lowered the formation of 7 alpha-hydroxycholesterol by rat liver microsomes, whereas Triton WR-1339 stimulated its production [20].

Gene context of C03594

• Cholesterol is superior to 7-ketocholesterol or 7 alpha-hydroxycholesterol as an allosteric activator for acyl-coenzyme A:cholesterol acyltransferase 1 [21].
• CONCLUSIONS: We conclude that the concentration of 7 alpha-hydroxycholesterol in serum is an indicator of bile acid synthesis and that serum levels of 7 alpha-hydroxycholesterol are not affected in patients treated with HMG-CoA reductase inhibitors but are affected in those treated with fenofibrate [22].
• A rapid method was developed to measure cholesterol 7 alpha-hydroxylase activity of hepatic microsomes by the direct determination of the mass of 7 alpha-hydroxycholesterol formed [23].
• Regulation of bile-acid synthesis. Role of sterol carrier protein 2 in the biosynthesis of 7 alpha-hydroxycholesterol [24].
• Microsomes immunotitrated with anti-SCP2 antibody exhibited considerably less capacity to synthesize 7 alpha-hydroxycholesterol, which was restored to control levels on addition of purified SCP2 [24].

Analytical, diagnostic and therapeutic context of C03594

• When administered to a human volunteer, labeled 24S-hydroxycholesterol was converted into bile acids at about half the rate of simultaneously administered labeled 7 alpha-hydroxycholesterol [25].
• When injected intravenously and followed by gas chromatography/mass spectrometry, 7 alpha-hydroxycholesterol was cleared at 23 times the rate of cholesterol [26].
• Use of HPLC for the determination of serum 7 alpha-hydroxycholesterol in cholestyramine-treated rats [27].
• The patients with preoperative external biliary drainage showed a higher serum 7 alpha-hydroxycholesterol level than those without biliary drainage before hepatectomy [28].
• Without infused 7 alpha-hydroxycholesterol, bile acids in the control group were composed mainly of beta-muricholic acid and to a lesser extent of cholic acid [29].

References