In vivo and in vitro metabolism of gomphoside, a cardiotonic steroid with doubly-linked sugar.
The metabolism of gomphoside, a cardiotonic steroid glycoside with doubly-linked 4,6-dideoxyhexosulose sugar was studied in vivo in rats, and in vitro using rat liver microsomes. The biliary excretion of metabolites, following intraperitoneal administrative of [3H]gomphoside, was rapid with 68% of radioactivity being collected over 8 h. The metabolites in the bile were principally a water-soluble glucuronide conjugate of gomphoside, and a small amount of chloroform-soluble metabolites. Conversion of [3H]gomphoside to metabolites by microsomes at 37 degrees C reached a maximum of 16% under optimum conditions, producing the same set of metabolites as those in the chloroform-soluble fraction of the bile. The major chloroform-soluble metabolite was the aglycone of gomphoside, viz. gomphogenin or 2 alpha,3 beta, 14-trihydroxy-5 alpha-card-20(22)-enolide. The other major component was recovered gomphoside. Other metabolites were calactin, calotropin, and 2 alpha-hydroxyuzarigenin 3-(4,6-dideoxy-beta-D-arabino-hexopyranoside). Another metabolite, which is a new cardenolide was shown to be 3-epi-gomphogenin or 2 alpha,3 alpha, 14-trihydroxy-5 alpha-card-20(22)-enolide. Gomphoside glucuronide was shown spectroscopically to have the glucuronide residue attached to position 3' of the hexosulose sugar. It was cleaved by beta-D-glucuronidase to gomphoside, and is thus gomphoside 3'-beta-D-glucuronide. The metabolic transformations of gomphoside are summarized in Fig. 5.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002298:Cardenolides / Q000378:metabolism*; D002301:Cardiac Glycosides / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D002298:Cardenolides; D002301:Cardiac Glycosides; D014316:Tritium; C053382:gomphoside