Hydroxymethylglutaryl-CoA reductase, a key enzyme in phytosterol synthesis?

Hydroxymethylglutaryl-CoA reductase (HMGR) regulates the synthesis of mevalonic acid (MVA), the precursor of the myriad of isoprenoid compounds functional in plant cells, with phytosterols representing one class of major importance. Recently, it has shown possible to solubilize and purify the membrane-bound enzyme from a heavy membrane fraction (P 16,000 x g) isolated from a cell-free homogenate of etiolated radish seedlings. What is presently known about the molecular and kinetic properties of radish HMGR is reported. Mevinolin, a highly specific competitive inhibitor of HMGR, has been valuable as a research tool in studying the regulatory role of HMGR activity for the growth and development of intact seedlings and cell cultures. The results obtained indicate a primary effect of mevinolin on phytosterol accumulation, whereas other endproducts of the multibranched isoprenoid pathway, such as ubiquinone in the mitochondria or chlorophylls and carotenoids in the plastids, are less or not at all affected. This and other data can be interpreted to mean that the organelles are autonomous in their capacity to synthesize MVA. Since the mevinolin-induced drop in free sterol accumulation is paralleled by significant plant growth retardation, a rate-limiting role of HMGR activity for phytosterol synthesis and normal development of plants is suggested.