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Additionally, cholesterol synthesis halted almost completely when the diet was cholesterol rich. Previous work had shown that cholesterol production within the body was controlled by a feedback mechanism in which cholesterol inhibited the enzyme b-hydroxy-b-methylglutaryl-CoA reductase (HMG Co-A reductase). By inhibiting this enzyme, the conversion of HMG-CoA to mevalonic acid was effectively blocked, and cholesterol synthesis was prevented (Figure 1). Drs. Endo and Kuroda, therefore, set forth attempting to discover a substance that would inhibit the action of HMG-CoA reductase.
Turning to the microbial world, the researchers hoped to identify a microorganism that produced an HMG-CoA reductase inhibitor as a defense mechanism against attack by other microbes, which rely on sterols as part of their biochemical make up...
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