Metabolism of exogenous galactosylceramide in the twitcher mouse brain.
The in vivo metabolism of galactosylceramide (gal-cer) in normal mice and in twitcher mice, a model of human GLD, was examined following intracerebral administration of gal-cer containing [1-14C] stearic acid. In normal mice, gal-cer was hydrolyzed to ceramide within 6 hours and ceramide was hydrolyzed to sphingosine and fatty acid. Most of the released fatty acid was immediately incorporated into other lipids. About 75% of injected gal-cer was hydrolyzed 80 hours after the injection, while in the twitcher mouse, only 17% of gal-cer was hydrolyzed. These results show that degradation of gal-cer is impaired in the twitcher mouse brain, but contradict to the fact that there was no evidence of any accumulation of gal-cer in the brain. This discrepancy may be due to the different sorting routes of biosynthesized and exogenously-administered gal-cer in the mouse brain. Most of the biosynthesized gal-cer is incorporated into myelin, while the injected gal-cer is incorporated into lysosomes.
Mitsuo
K
K
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kobayashi
T
T
Shinnoh
N
N
Goto
I
I
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002554:Cerebrosides / Q000493:pharmacokinetics*; D005699:Galactosylceramides / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000378:metabolism*
D002554:Cerebrosides; D005699:Galactosylceramides