摘要: Bile acids are important physiological agents required for disposal of cholesterol and absorption vitamins fats. synthesized from in the liver. Enterohepatic circulation bile is very efficient plays an role lipid secretion, regulation acid biosynthesis homeostasis. Conversion to requires 15 different enzymatic steps. Four cytochrome P450 enzymes play roles biosynthesis. The classic pathway starts with modification sterol ring followed by side chain cleavage reactions synthesize cholic (CA) chenodeoxycholic (CDCA), primary most species. first rate-limiting enzyme this 7alpha -hydroxylase, a microsomal P450, CYP7A. Another 12alpha-hydroxylase (CYP12) synthesis acid. Mitochondrial 27-hydroxylase (CYP27) catalyzes oxidation convert C27 C24 acids. An alternative (acidic) has been known sometime but only recently attracted much attention. In pathway, precedes ring. reaction 7alpha-hydroxylation catalyzed oxysterol 7alpha-hydroxylase (CYP7B). Recent advances purification cloning these major pathways have led better understanding molecular basis pathways.
bioscience.org
researchgate.net 参考文章(143)
H M Princen, P Meijer, B Hofstee, Dexamethasone regulates bile acid synthesis in monolayer cultures of rat hepatocytes by induction of cholesterol 7 alpha-hydroxylase Biochemical Journal. ,vol. 262, pp. 341- 348 ,(1989) , 10.1042/BJ2620341
J Twisk, E M Lehmann, H M G Princen, Differential feedback regulation of cholesterol 7α-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes Biochemical Journal. ,vol. 290, pp. 685- 691 ,(1993) , 10.1042/BJ2900685
P F Johnson, Transcriptional activators in hepatocytes. Cell Growth & Differentiation. ,vol. 1, pp. 47- 52 ,(1990)
S Andersson, D L Davis, H Dahlbäck, H Jörnvall, D W Russell, Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. Journal of Biological Chemistry. ,vol. 264, pp. 8222- 8229 ,(1989) , 10.1016/S0021-9258(18)83172-6
D. Stroup, J. Y. L. Chiang, Identification and characterization of a putative bile acid-responsive element in cholesterol 7 alpha-hydroxylase gene promoter. Journal of Biological Chemistry. ,vol. 269, pp. 17502- 17507 ,(1994) , 10.1016/S0021-9258(17)32469-9
R.T. Stravitz, P.B. Hylemon, D.M. Heuman, L.R. Hagey, C.D. Schteingart, H.T. Ton-Nu, A.F. Hofmann, Z.R. Vlahcevic, Transcriptional regulation of cholesterol 7 alpha-hydroxylase mRNA by conjugated bile acids in primary cultures of rat hepatocytes. Journal of Biological Chemistry. ,vol. 268, pp. 13987- 13993 ,(1993) , 10.1016/S0021-9258(19)85199-2
M S Straka, L H Junker, L Zacarro, D L Zogg, S Dueland, G T Everson, R A Davis, Substrate stimulation of 7 alpha-hydroxylase, an enzyme located in the cholesterol-poor endoplasmic reticulum. Journal of Biological Chemistry. ,vol. 265, pp. 7145- 7149 ,(1990) , 10.1016/S0021-9258(19)39091-X
P.B. Hylemon, E.C. Gurley, R.T. Stravitz, J.S. Litz, W.M. Pandak, J.Y. Chiang, Z.R. Vlahcevic, Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures. Journal of Biological Chemistry. ,vol. 267, pp. 16866- 16871 ,(1992) , 10.1016/S0021-9258(18)41864-9
N B Javitt, R Pfeffer, E Kok, S Burstein, B I Cohen, K Budai, Bile acid synthesis in cell culture. Journal of Biological Chemistry. ,vol. 264, pp. 10384- 10387 ,(1989) , 10.1016/S0021-9258(18)81631-3
Roberta Hall, Engeline Kok, Norman B. Javitt, Bile acid synthesis: down-regulation by monohydroxy bile acids The FASEB Journal. ,vol. 2, pp. 152- 156 ,(1988) , 10.1096/FASEBJ.2.2.3342968