Biomaterial Database

Potential bile acid precursors in plasma--possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. 1990

M Axelson, and J Sjövall

Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden.

The plasma concentrations of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid have been compared with that of 7 alpha-hydroxy-4-cholesten-3-one in healthy subjects and in patients with an expected decrease or increase of the bile acid production. In controls and patients with liver disease, the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid was positively correlated to that of 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and not to that of 7 alpha-hydroxy-4-cholesten-3-one. In patients with stimulated bile acid formation the levels of the acids were not correlated to each other but there was a significant positive correlation between the levels of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid and 7 alpha-hydroxy-4-cholesten-3-one. These findings indicate that the precursor of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid differs depending on the activity of cholesterol 7 alpha-hydroxylase. Since the activity of this enzyme is reflected by the level of 7 alpha-hydroxy-4-cholesten-3-one in plasma the findings are compatible with a formation of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid from 3 beta,7 alpha-dihydroxy-5-cholestenoic acid when the rate of bile acid formation is normal or reduced and from 7 alpha-hydroxy-4-cholesten-3-one under conditions of increased bile acid synthesis. In support of this interpretation, 7 alpha,26-dihydroxy-4-cholesten-3-one was identified at elevated levels in plasma from patients with ileal resection or treated with cholestyramine. The levels of 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one were also higher than normal in these patients. Based on these findings and previous knowledge, a model is proposed for the biosynthesis of bile acids in man. Under normal conditions, two major pathways, one "neutral" and one "acidic" or "26-oxygenated", lead to the formation of cholic acid and chenodeoxycholic acid, respectively. These pathways are separately regulated. When the activity of cholesterol 7 alpha-hydroxylase is high, the "neutral" pathway is most important whereas the reverse is true when cholesterol 7 alpha-hydroxylase activity is low. In cases with enhanced activity of cholesterol 7 alpha-hydroxylase, the "neutral" pathway is connected to the "acidic" pathway via 7 alpha,26-dihydroxy-4-cholesten-3-one, whereas a flow from the acidic pathway to cholic acid appears to be of minor importance.

UI	MeSH Term	Description	Entries
D007408	Intestinal Absorption	Uptake of substances through the lining of the INTESTINES.	Absorption, Intestinal
D008107	Liver Diseases	Pathological processes of the LIVER.	Liver Dysfunction,Disease, Liver,Diseases, Liver,Dysfunction, Liver,Dysfunctions, Liver,Liver Disease,Liver Dysfunctions
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002635	Chenodeoxycholic Acid	A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.	Chenic Acid,Chenodeoxycholate,Chenodiol,Gallodesoxycholic Acid,Chenique Acid,Chenix,Chenofalk,Chenophalk,Henohol,Quenobilan,Quenocol,Sodium Chenodeoxycholate,Acid, Chenic,Acid, Chenique,Acid, Chenodeoxycholic,Acid, Gallodesoxycholic,Chenodeoxycholate, Sodium
D002782	Cholestenes	Steroids with methyl groups at C-10 and C-13 and a branched 8-carbon chain at C-17. Members include compounds with any degree of unsaturation; however, CHOLESTADIENES is available for derivatives containing two double bonds.
D002783	Cholestenones	CHOLESTENES with one or more double bonds and substituted by any number of keto groups.
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D002790	Cholesterol 7-alpha-Hydroxylase	A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.	CYP7,CYP7A,Cytochrome P-450 CYP7,CYP 7,CYP 7A,Cholesterol 7-alpha-Monooxygenase,Cholesterol 7alpha-Hydroxylase,Cholesterol-7-Hydroxylase,Cytochrome P450 7,Cholesterol 7 Hydroxylase,Cholesterol 7 alpha Hydroxylase,Cholesterol 7 alpha Monooxygenase,Cholesterol 7alpha Hydroxylase,Cytochrome P 450 CYP7