The Glucuronic Acid Conjugation of Acyclic Aliphatic Alcohols
     

    Kamil, Smith and Williams (1952) investigated the conjugation of higher alcohols with glucuronic acid. Higher alcohols, also called fusel oil, occur in small amounts in wines and liquors. These alcohols, which include n-propanol, isopropanol, n-butanol, isobutanl, n-, active and iso-amyl alcohols, are of toxicological interest. The bouquet or flavor of wines is in part due to the presence of esters of these alcohols. The authors stated that appreciable quantities of higher alcohols are constantly consumed by human beings. However, in most of the studies on alcohols scientists have rarely given attention to whether these higher alcohols give rise to conjugated glucuronic acids. In their study, Kamil, Smith and Williams addressed the question to what extent various monhydric aliphatic (open chain structure) alcohols conjugate with glucuronic acid in the rabbit and how the findings relate to the structure and property of the alcohol.

    A variety of alcohols of laboratory reagent quality was obtained from commercial sources. Large chinchilla rabbits of about 3 kg weight were kept on a constant diet for at least a week before administration of alcohol. Alcohols were administered with water by stomach tube and the glucuronic acid output for each alcohol was determined simultaneously on three animals. The crude glucuronides of the various alcohols were isolated from the urine by extraction with ether or mixtures of ether and ethanol. The glucuronides were then first methylated, then acetylated and optical rotations were tabulated. A total of thirty aliphatic alcohols was studied.

    Kamil, Smith and Williams found that the conjugation of normal primary alcohols was relatively low, less than 10% of the administered dose. Alcohols listed in this category included methyl, ethyl, n-hexyl and isoamyl. Conjugation of secondary alcohols increased with increasing number of carbon atoms in the molecule from 10% with isopropanol to 60-70% for the secondary heptyl alcohols. The oxydation products of some of the secondary alcohols was shown to be ketones. The conjugation of three tertiary alcohols, butyl, amyl and hexyl, was higher than that of the corresponding primary and secondary alcohols. According to the authors the results suggested that conjugation is an alternative metabolic process to oxidation. The order of conjugation was tertiary>secondary>primary which is the reverse order for ease of oxidation. The authors believe their work indicated that the metabolic path for the elimination of aliphatic alcohols - oxydation, conjugation or unchanged in expired air or urine - depends primarily on chemical factors, such as the number of carbon atoms, nature of the hydroxyl group and the extent of branching of the hydrocarbon chain.

    Kamil IA, Smith JN and Williams RT. The metabolism of aliphathic alcohols. The glucuronic acid conjugation of acyclic alipathic alcohols. Biochem J. 1952:53. 129-136


    Last updated 2/21/2000