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Pathway Description
Bile Acid Biosynthesis
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-15
A bile acids life begins as cholesterol is catabolized, as bile acid is a derivative of cholesterol. This pathway occurs in the liver, beginning with cholesterol being converted to 7a-hydroxycholesterol through the enzyme cholesterol-7-alpha-monooxygenase, after being transported into the liver cell. 7a-hydroxycholesterol then becomes 7a-hydroxy-cholestene-3-one, which is made possible by the enzyme 3-beta-hydroxysteroid dehydrogenase type 7. 7a-hydroxy-cholestene-3-one then is used in two different chains of reactions. The first, continuing in the liver, uses the enzyme 3-oxo-5-beta-steroid-4-deydrogenase to become 7a-hydroxy-5b-cholestan-3-one. After that, aldo-keto reductase family 1 member C4 is used to create 3a,7a-dihydroxy-5b-cholestane. In the mitochondria of the cell, sterol 26-hydroxylase converts 3a,7a-dihydroxy-5b-cholestane to 3a,7a,26-trihydroxy-5b-cholestane, which is then converted to 3a,7a-dihydroxy-5b-cholestan-26-al by the same enzyme used in the previous reaction. This enzyme is used another time, to create 3a,7a-dihydroxycoprostanic acid. Then, bile acyl-CoA synthetase teams up with 3a,7a-dihydroxycoprostanic acid to create 3a,7a-dihydroxy-5b-cholestanoyl-CoA. 3a,7a-dihydroxy-5b-cholestanoyl-CoA remains intact while alpha-methylacyl-CoA racemase moves it along through the peroxisome. Peroxisomal acyl coenzyme A oxidase 2 converts 3a,7a-dihydroxy-5b-cholestanoyl-CoA into 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA. With the help of water, peroxisomal multifunctional enzyme type 2 turns 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA into 3a,7a,24-trihydoxy-5b-cholestanoyl-CoA. This compound then uses peroxisomal multifunctional enzyme type 2 to create chenodeoxycholoyl-CoA. From there, propionyl-CoA and chenodeoxycholoyl-CoA join forces and enlist the help of non-specific lipid transfer protein to further chenodeoxycholoyl-CoAâ€TMs journey in the peroxisome. It is then transported back into intracellular space, where after its used in 3 different reactions, its derivatives interact with intestinal microflora in the extracellular space to become lithocholyltaurine, lithocholic acid glycine conjugate, and lithocholic acid. Revisiting 7a-hydroxy-cholestene-3-one, the second chain of reactions it is involved in follows a similar path as the first, moving through the mitochondria, endoplasmic reticulum and peroxisome until choloyl-CoA is formed, which then is used in three reactions so that its derivatives may leave the cell to interact with intestinal microflora and become taurodeoxycholic acid, deoxycholic acid glycine conjugate and deoxycholic acid. There are two more important components of this pathway, both depicting the breakdown of cholesterol into bile acid. These components of the pathway occur in the endoplasmic reticulum membrane, although 2 enzymes, 25-hydroxycholesterol 7-alpha-hydroxylase and sterol 26 hydroxylase, are found in the mitochondria. Bile acids play a very important part in the digestion of foods, and are responsible for the absorption of water soluble vitamins in the small intestine. Bile acids also help absorb fats into the small intestine, a crucial part of any vertebrates diet.
References
Bile Acid Biosynthesis References
Morohashi K, Fujii-Kuriyama Y, Okada Y, Sogawa K, Hirose T, Inayama S, Omura T: Molecular cloning and nucleotide sequence of cDNA for mRNA of mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4647-51. doi: 10.1073/pnas.81.15.4647.
Pubmed: 6589615
Chashchin VL, Lapko VN, Adamovich TB, Lapko AG, Kuprina NS, Akhrem AA: Primary structure of the cholesterol side-chain cleavage cytochrome P-450 from bovine adrenocortical mitochondria and some aspects of its functioning on a structural level. Biochim Biophys Acta. 1986 Jun 5;871(2):217-23. doi: 10.1016/0167-4838(86)90176-7.
Pubmed: 3518802
Ogishima T, Okada Y, Kominami S, Takemori S, Omura T: Partial amino acid sequences of two mitochondrial and two microsomal cytochrome P-450's from adrenal cortex. J Biochem. 1983 Nov;94(5):1711-4.
Pubmed: 6654880
Westerman J, Wirtz KW: The primary structure of the nonspecific lipid transfer protein (sterol carrier protein 2) from bovine liver. Biochem Biophys Res Commun. 1985 Feb 28;127(1):333-8. doi: 10.1016/s0006-291x(85)80163-7.
Pubmed: 3977925
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
Zhao HF, Simard J, Labrie C, Breton N, Rheaume E, Luu-The V, Labrie F: Molecular cloning, cDNA structure and predicted amino acid sequence of bovine 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4 isomerase. FEBS Lett. 1989 Dec 18;259(1):153-7. doi: 10.1016/0014-5793(89)81516-9.
Pubmed: 2599102
Rutherfurd KJ, Chen SA, Shively JE: Isolation and amino acid sequence analysis of bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase. Biochemistry. 1991 Aug 20;30(33):8108-16. doi: 10.1021/bi00247a003.
Pubmed: 1868086
Hara S, Miyata A, Yokoyama C, Inoue H, Brugger R, Lottspeich F, Ullrich V, Tanabe T: Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells. J Biol Chem. 1994 Aug 5;269(31):19897-903.
Pubmed: 8051072
Pereira B, Wu KK, Wang LH: Molecular cloning and characterization of bovine prostacyclin synthase. Biochem Biophys Res Commun. 1994 Aug 30;203(1):59-66. doi: 10.1006/bbrc.1994.2148.
Pubmed: 8074709
Pereira B, Wu KK, Wang LH: Bovine prostacyclin synthase: purification and isolation of partial cDNA. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1041-8. doi: 10.1006/bbrc.1993.2583.
Pubmed: 8280118
Timmermans MY, Teuchy H, Kupers LP: The cDNA sequence encoding bovine pregastric esterase. Gene. 1994 Sep 30;147(2):259-62. doi: 10.1016/0378-1119(94)90077-9.
Pubmed: 7926811
Timmermans MY, Reekmans G, Teuchy HJ, Kupers LP: Inhibition studies on calf pregastric esterase: the enzyme has no functional thiol group. Biochem J. 1996 Mar 15;314 ( Pt 3):931-6. doi: 10.1042/bj3140931.
Pubmed: 8615791
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000035
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