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J. Biochem, 1988, Vol. 104, No. 1 87-92
© 1988 Japanese Biochemical Society

research-article

Metabolism of Exogenous Gangliosides GM1 and Chemically Modified GM1 in Mice1

Kiyoshi Ogura and Shizuo Handa

Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University Bunkyo-ku, Tokyo 113

Ganglioside GM1(NeuAc), labeled at the C-3 position of sphingosine with tritium, was injected into C3H/He,C57BL/1O, B1O.AQR mice intraperitoneally. The incorporation and the distribution of the radioactivity in various organs were examined. The injected [3H]GM1(NeuAc) was mainly incorporated in the liver and hydrolyzed sequentially. Sialic acid of ganglioside GM1(NeuAc) and metabolites was converted to N-glycolyl type from N-acetyl type. An appreciable amount of the sphingosine moiety in the administered GM1(NeuAc), moreover, was reutilized, being converted to sphingomyelin, and incorporated into alkyl chain of the ether lipid in phosphatidylethanolamine. The distributions of radioactivity in the metabolites of GM1(NeuAc) administered to the three strains of mice were different from each other. In other organs, GM1(NeuAc) was incorporated and metabolized only slightly. The N-methylamide, at the carboxyl group of the sialic acid, of the labeled gangliosideGM1 (GM1(NeuAc)-NMe) was injected into C3H/He mice. Most of the administered [3H]GM1(NeuAc)-NMe was incorporated in the liver, and was metabolized to GM3(NeuAc)-NMe, via GM2(NeuAc)-NMe, within24 h. GM3(NeuAc)-NMe was the only radioactive compound in the subsequent 10 weeks, but disappeared from the liver gradu ally. N-Methylamide-modified gangliosides were resistant to hydrolysis by mouse hepatic sialidase, to elongation by glycosyltransferase and to N-glycolylation at N-acetyl-neuraminic acid by monooxygenase.

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and some of the results were presented at the 28th and 29th Annual Meetings of the Japanese Conference on the Biochemistry of Lipids (July 1986, Nagoya; and July 1987, Tokushima, respectively).


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