scholarly journals Regulation of bile-acid synthesis. Role of sterol carrier protein2 in the biosynthesis of 7α-hydroxycholesterol

1985 ◽  
Vol 230 (1) ◽  
pp. 19-24 ◽  
Author(s):  
H Seltman ◽  
W Diven ◽  
M Rizk ◽  
B J Noland ◽  
R Chanderbhan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Gas Chromatography Mass Spectrometry ◽  
Rat Liver Microsomes ◽  
Rate Limiting Step ◽  
Rate Limiting

Sterol carrier protein2 (SCP2) is known to stimulate utilization of cholesterol in enzymic reactions in which cholesterol is the substrate. Substantial recent experimental evidence indicates that SCP2: activates enzymic conversion of intermediates between lanosterol and cholesterol; stimulates the microsomal conversion of cholesterol into cholesterol ester in rat liver; and enhances mitochondrial utilization of cholesterol for pregnenolone formation in the adrenals. The conversion of cholesterol into 7 α-hydroxycholesterol is the rate-limiting step in bile-acid synthesis. We therefore investigated the effect of SCP2 on this physiologically critical reaction by using a gas-chromatography-mass-spectrometry procedure that measures the mass of 7 α-hydroxycholesterol formed. The results show that SCP2 enhances 7 α-hydroxycholesterol formation by rat liver microsomes (microsomal fractions), utilizing either endogenous membrane cholesterol, cholesterol supplied exogenously in serum or in the form of cholesterol/phospholipid liposomes. Microsomes immunotitrated with anti-SCP2 antibody exhibited considerably less capacity to synthesize 7 α-hydroxycholesterol, which was restored to control levels on addition of purified SCP2. These data are consistent with the suggestion that SCP2 may be of physiological significance in the overall metabolism of cholesterol.

scholarly journals Study of Changes in Cholesterol 7 Alpha Hydroxylase in Patients with Gall Stone in Babylon Province

2018 ◽  
Vol 26 (4) ◽  
pp. 198-203
Author(s):  
Samah Sajad Kadim ◽  
Mohammad O. Al-Mohammadi ◽  
Ali K. Shaaeli
Keyword(s):  
Bile Acid ◽  
Gallstone Disease ◽  
Gall Stone ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Gallbladder Motility ◽  
Major Health Problem ◽  
Major Health ◽  
Rate Limiting Step ◽  
Rate Limiting

The gallbladder (GB) is an assistant organ of the digestive system, It is  located under the liver and attached to the biliary system, And it is responsible for controlling release of bile and the storage. Gallstone disease a major health problem worldwide. In 10–15% of adults contain gallstone disease. This study (case control) consists of  one hundred sixty (160) patients are included in this study randomly selected  and consisted of 130 females and 30 males. All patients are examined 24 hr. Before operation, Intra operatively and 24hr post operatively. Decreased gallbladder motility and the decrease of cholesterol 7 –alpha hydroxylase activity, which regulate the novo bile salt synthesis. The rate-limiting step of bile acid synthesis is acting between the liver-specific CYP 7A1 (CYP450). Thus, Alteration in CYP gene control also has an impact on bile acid synthesis and lipid metabolism.

In Vitro Metabolism of E2, G2: Novel Bile Acid-Coupling Camptothecin Analogues, in Rat Liver Microsomes

2021 ◽  
Vol 16 ◽  
Author(s):  
Xiangli Zhang ◽  
Qin Shen ◽  
Yi Wang ◽  
Leilei Zhou ◽  
Qi Weng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Phase I ◽  
Rat Liver ◽  
Deoxycholic Acid ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Rat Liver Microsomes ◽  
Camptothecin Analogues

Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).

scholarly journals Transport of Cholesterol into Mitochondria Is Rate-limiting for Bile Acid Synthesis via the Alternative Pathway in Primary Rat Hepatocytes

2002 ◽  
Vol 277 (50) ◽  
pp. 48158-48164 ◽  
Author(s):  
William M. Pandak ◽  
Shunlin Ren ◽  
Dalila Marques ◽  
Elizabeth Hall ◽  
Kaye Redford ◽  
...  
Keyword(s):  
Bile Acid ◽  
Alternative Pathway ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Primary Rat Hepatocytes ◽  
Rate Limiting

scholarly journals Study on Stereospecificity of Enzyme Reaction Related to Peroxisomal Bile Acid Synthesis in Rat Liver.

1992 ◽  
Vol 40 (2) ◽  
pp. 446-448 ◽  
Author(s):  
Yasumasa KOIBUCHI ◽  
Junji YAMADA ◽  
Takafumi WATANABE ◽  
Takao KUROSAWA ◽  
Sadahiko TOHMA ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Enzyme Reaction ◽  
Acid Synthesis ◽  
Bile Acid Synthesis
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