Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat

Journal Article · Sun May 01 00:00:00 EDT 1988 · Hepatol.; (United States)

DOI:https://doi.org/10.1002/hep.1840080329· OSTI ID:7140989

Duane, W C; Bjoerkhem, I H; Hamilton, J N; Mueller, S M

During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. In the present study, we have quantitated the relative importance of these two pathways in vivo by measuring production of (14C) acetone from (14C)-26-cholesterol. Four days after intraperitoneal injection of 20 to 40 muCi (14C)-26-cholesterol and 1 day after beginning a constant intravenous infusion of unlabeled acetone at 25 mumoles per kg per min, 6 male and 2 female Sprague-Dawley rats underwent breath collections. Expired acetone was trapped and purified as the 2,4-dinitrophenylhydrazine derivative. 14CO2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied times the acetone infusion rate to calculate production of (14C)acetone. (14C) Acetone production averaged 1.7% of total release of 14C from (14C)-26-cholesterol, estimated by 14CO2 output. The method was validated by showing that (14C) acetone production from (14C)isopropanol averaged 111% of the (14C)isopropanol infusion rate. We conclude that, in the normal rat, the 25-hydroxylation pathway accounts for less than 2% of bile acid synthesis.

• Research Organization: Veterans Administration Medical Center, Minneapolis, MN (USA)
• OSTI ID: 7140989
• Journal Information: Hepatol.; (United States), Vol. 8:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BILE ACIDS
BIOSYNTHESIS
HYDROXYLATION
ACETONE
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
CARBON DIOXIDE
CHOLESTEROL
RATS
TRACER TECHNIQUES
ANIMALS
CARBON COMPOUNDS
CARBON OXIDES
CARBOXYLIC ACIDS
CHALCOGENIDES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
RODENTS
STEROIDS
STEROLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques