Xenobiotic Metabolism

Oswald Schmiedeberg

Conjugation: Glucuronides

The history of glucuronide discovery is complex since identification of the conjugating moiety—glucuronic acid—required extensive isolation work followed by the appropriate sugar chemistry. While M. Jaffe often received credit for the discovery of glucuronic acid, the definitive characterization was detailed by O. Schmiedeberg and H. Meyer.

The first compound characterized as a sugar conjugate was euxanthic acid, a major component of Indian yellow dye. Baeyer characterized the aglycone of euxanthic acid as euxanthone and the sugar moiety as an oxidized glucose derivative. In the 1870's other sugar-containing metabolites were isolated from urine. Von Mering and Musculus isolated urochloralic acid from the urine of humans given chloral hydrate while Jaffe, studying nitrotoluene metabolism in dogs, found that o-nitrotoluene gave rise to o-nitrobenzyl alcohol excreted as a conjugate. Jaffe concluded that the sugar moiety was a carboxylic acid derivative of glucose.

Schmiedeberg and Meyer followed up on early studies of camphor metabolism and isolated a camphor conjugate from the urine of dogs dosed with camphor. They isolated and characterized the sugar moiety as glucuronic acid.

Schmid had characterized the formation of euxanthic acid as occurring through “the vital process.” It wasn't until 1953 that this process was elucidated through Dutton and Story's discovery of uridine diphosphoglucuronic acid (UDPGA) and their elaboration of the role of the co-factor in glucuronide formation.

Indian yellow dye was traditionally isolated from the urine of cows fed mango leaves. Erdmann observed that euxanthic acid could be hydrolyzed by acid to yield the aglycone. In 1855 Schmid reported that euxanthic acid was excreted by camels fed the fruits of Mangostana Mangifer.

BAS Home