Incorporation and metabolism of exogenous G(M1) ganglioside in rat liver

The pathways of metabolic processing of exogenously administered G(M1) ganglioside in rat liver was investigated at the subcellular level. The G(M1) used was ³H-labelled at the level of long-chain base ([Sph(sphingosine)-³H]G(M1)) or of terminal galactose ([Gal-³H)G(M1)). The following radioactive compounds, derived from exogenous G(M1), were isolated and chemically characterized: gangliosides G(M2), G(M3), G(D1a) and G(D1b) {nomenclature of Svennerholm [(1964) J. Lipid Res. 5, 145-155] and IUPAC-IUB Recommendations [(1977) Lipids 12, 455-468]}; lactosylceramide, glucosylceramide and ceramide; sphingomyelin. G(M2), G(M3), lactosylceramide, glucosylceramide and ceramide, relatively more abundant shortly after G(M1) administration, were mainly present in the lysosomal fraction and reflected the occurrence of a degradation process. ³H₂O was also produced in relevant amounts, indicating complete degradation of G(M1), although no free long-chain bases could be detected. G(D1a) and G(D1b), relatively more abundant later on later administration, were preponderant in the Golgi-apparatus fraction and originated from a biosynthetic process. More G(D1a) was produced starting from [Sph-³H]G(M1) than from [Gal-³]G(M1), and radioactive G(D1b) was present only after [Sph-³H]G(M1) injection. This indicates the use of two biosynthesis routes, one starting from a by-product of G(M1) degradation, the other implicating direct sialylation of G(M1). Both routes were used to produce G(D1a), but only the first one for producing G(D1b). Sphingomyelin was the major product of G(M1) processing, especially at the longer times after injection, and arose from a by-product of G(M1) degradation, most likely ceramide.