Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat.
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.
D000433:1-Propanol / Q000378:metabolism; D000096:Acetone / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006900:Hydroxylation; D008297:Male; D010659:Phenylhydrazines / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D010659:Phenylhydrazines; D011422:Propionates; D000096:Acetone; D002245:Carbon Dioxide; C004787:2,4-dinitrophenylhydrazine; D000433:1-Propanol; D002784:Cholesterol; C029658:propionic acid