THE EFFECTS OF EXCESS EXOGENOUS MEVALONIC ACID ON STEROL AND STERYL ESTER BIOSYNTHESIS IN CELERY (APIUM-GRAVEOLENS) CELL-SUSPENSION CULTURES

Cell suspension cultures of celery (Apium graveolens) have been used t o investigate the fate of excess added mevalonic acid and the effects on the amounts of free sterols and steryl esters in the cells. Radiola belling studies using [2-C-14] MVA showed that the main effect of exce ss MVA (5 mM) was an increase in the synthesis of steryl esters. Furth er analysis revealed that esterified 4,4-dimethylsterols were more hig hly labelled than 4-mono- and 4-desmethylsterols in MVA-treated cells, suggesting a restriction in the flow of carbon downstream from cycloa rtenol and 24-methylenecycloartanol, and thus indicating the presence of a post-mevalonic acid control point in the sterol biosynthesis path way. The total fatty acids recovered from the celery cell lipids showe d a very low incorporation of radioactivity from the [2-C-14] mevalona te, indicating that a limited breakdown of excess mevalonate to acetat e may occur in these cells, possibly by the operation of the mevalonat e shunt. However, this does not appear to be a major route for the dis posal of excess mevalonate. Analysis of the free sterols and steryl es ters showed that the administration of excess exogenous MVA (5 mM) to Apium graveolens cells caused a two-fold increase in the steryl ester content when compared with control cells, although there was little ef fect on the free sterol content or composition. When excess MVA was ad ministered in conjunction with the sterol biosynthesis inhibitor paclo butrazol (50 mu M), the steryl ester content increased almost three-fo ld. It is possible that, as well as providing a means of storage of ex cess sterols, the esterification of sterols may have a regulatory role in sterol biosynthesis, by controlling the rate of C-4 demethylation of precurser 4,4-dimethylsterols