REGULATION OF GLYCOLIPID BIOSYNTHESIS - EFFECTS OF VIRUS-INFECTION AND DRUG-INDUCED TRANSLATIONAL INHIBITION ON GLYCOLIPID METABOLISM

Suppression of HeLa cell protein synthesis by either viral infection or translation-inhibiting drugs induces alterations of cell glycolipid concentrations such that there is accumulation of the simple glycolipid species (mono- and diglycosylceramides) as well as a depletion of the more complex ones (triglycosylceramides and gangliosides). In addition, the cellular pool of free ceramides is increased two-to threefold over that found in control cells. The in vitro activities of UDP-glucose:ceramide glucosyltransferase and UDP-galactose:glucosylceramide galactosyltransferase in homogenates prepared from streptovitacin A treated HeLa cells were found to decline progressively with increasing times of drug treatment when exogenous ceramide or glucosyl- cerarnide was utilized as carbohydrate acceptor. However, if endogenous ceramide was used as glucose acceptor, the activity of UDP-glucose:ceramide glucosyltransferase in homogenates from cells pretreated for 6 h with translational inhibitor was approximately twofold higher than that found in control cell homogenates, presumably as a result of the increased ceramide concentration in drug-treated cells. The source of increased ceramide in such cells is uncertain but does not appear to be derived from an impairment of ceramide incorporation into sphingomyelin. The results suggest that one component of cellular control of glycolipid biosynthesis may be the regulation of free ceramide levels. © 1979, American Chemical Society. All rights reserved.