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Effects of Coffee and Caffeine Consumption on Serum Lipids and Lipoproteins
Published in Barry D. Smith, Uma Gupta, B.S. Gupta, Caffeine and Activation Theory, 2006
Ming Wei, Harvey A. Schwertner
Post, de Wit, and Princen (1997) studied the effects of cafestol and a mixture of cafestol, kahweol, and isokahweol (5 w/w) (Jacobsen & Thelle, 1987b; Jansen et al., 1995) on bile acid synthesis and on cholesterol 7-alpha-hydroxylase and sterol 27-hydroxylase activities in cultured rat hepatocytes. Dose-dependent decreases in bile acid mass production, cholesterol 7 alpha-hydroxylase activities, and sterol 27-hydroxylase activities were found when 20 μg/ml of cafestol was given. Maximal reductions of bile acid mass production, cholesterol 7 alpha-hydroxylase activities, and sterol 27-hydroxylase activities were −91, −79, and −49%, respectively. The mixture of cafestol, kahweol, and isokahweol was less potent in suppression of bile acid synthesis and cholesterol 7-alpha-hydroxylase activity. LDL-receptor, HMG-CoA reductase, and HMG-CoA synthase mRNAs were also significantly decreased by cafestol (−18, −20, and −43%, respectively).
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
383-392, 1998. Tzung, K.W., Ishimura-Oka, K., Kihara, S., Oka, K., and Chan, L., Structure of the mouse cholesterol 7 alpha-hydroxylase gene, Genomics, 21, 244-247, 1994.Wood, A.W., Ryan, D.E., Thomas, P.E., and Levin, W., Regio- and stereoselective metabolism of two C19 steroids by five highly purified and reconstituted rat hepatic
Odevixibat: an investigational inhibitor of the ileal bile acid transporter (IBAT) for the treatment of biliary atresia
Published in Expert Opinion on Investigational Drugs, 2022
Bile acids are subject to enterohepatic circulation, production and reabsorption are tightly regulated (Figure 1). These are converted from cholesterol to primary bile acids, mainly cholic acid (CA) and chenodeoxycholic acid (CDCA) in hepatocytes in a multi-step process, followed by conjugation with taurine or glycine [10]. The first and rate limiting enzyme for biosynthesis is cholesterol 7 alpha-hydroxylase, encoded by CYP7A1 [11]. Subsequently, bile acids are actively secreted across the apical canalicular membrane of the hepatocyte by the bile salt export pump (BSEP) into the canaliculus [12]. Food intake leads to a contraction of the gallbladder via the release of cholecystokinin [13], which later causes bile to be secreted into the small intestine, enabling the absorption of lipids, including fat-soluble vitamins and cholesterol [14]. Secondary bile acids, deoxycholic acid (DCA), and lithocholic acid (LCA), result from the metabolism of bacteria within the intestine [15,16]. Reabsorption of bile acids occurs via the ileal bile acid transporter (IBAT), also called the apical sodium-dependent bile acid transporter (ASBT), mainly expressed in the terminal ileum [14,17]. This process is highly effective, as over 90% of bile acids are recycled [14]. They are then exported through the basolateral membrane of enterocytes to be released in the portal circulation by the heteromeric organic solute transporter (OST), OSTα-OSTβ [17]. With their arrival at the liver, they are taken up by the Na+-taurocholate co-transporting polypeptide (NTCP), a transporter protein located in the basolateral membrane of the hepatocyte and can reenter enterohepatic circulation by resecretion into the bile through BSEP.