Metabolism of intravenously administered 7 alpha-hydroxycholesterol-3 beta-stearate in the hamster.
In order to investigate the metabolic fate of serum esterified 7 alpha-hydroxycholesterol, [4-14C]7 alpha-hydroxycholesterol-3 beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 +/- 5.7% (48.7-66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 +/- 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 +/- 8.6% (63.3-90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3 alpha-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha-hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7 alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile.
Kishinaka
M
M
Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Kosahara
K
K
Okamoto
S
S
Oda
H
H
Ichimiya
H
H
Chijiiwa
K
K
Kuroki
S
S
D000818:Animals; D001646:Bile / Q000378:metabolism; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D008647:Mesocricetus; D013228:Stearates / Q000097:blood / Q000378:metabolism*
D006888:Hydroxycholesterols; D013228:Stearates; C078511:7-hydroxycholesterol-3-stearate; C011724:cholest-5-en-3 beta,7 alpha-diol