COQ10B Inhibitors

Chemical inhibitors of COQ10B function primarily by reducing the availability of substrates necessary for its role in the biosynthesis of coenzyme Q10 (CoQ10). Statins, a class of chemicals including atorvastatin, simvastatin, rosuvastatin, lovastatin, pravastatin, fluvastatin, cerivastatin, pitavastatin, and mevastatin, operate by inhibiting the enzyme HMG-CoA reductase. This enzyme is crucial in the mevalonate pathway, which is the upstream process for the synthesis of several important molecules, including CoQ10. By inhibiting HMG-CoA reductase, statins limit the production of mevalonate and its derivatives, which are required substrates for the function of COQ10B in the biosynthesis of CoQ10. Consequently, these statins functionally inhibit COQ10B by creating a substrate deficiency for its enzymatic activity, effectively hampering the synthesis of CoQ10. Other chemical inhibitors interfere with different enzymes that are part of or associated with the biosynthetic pathway of CoQ10. For example, aminobenzotriazole is a broad-spectrum cytochrome P450 inhibitor that can prevent the post-translational modifications necessary for the proper function of COQ10B. By inhibiting these modifications, aminobenzotriazole can functionally inhibit COQ10B activity. Diphenyleneiodonium chloride targets flavoenzymes, which are potentially involved in electron transfer processes essential for CoQ10 biosynthesis. Inhibition of these enzymes can disrupt the electron transfer necessary for COQ10B's enzymatic activity, resulting in functional inhibition. Additionally, terbinafine inhibits squalene epoxidase, an enzyme upstream in the cholesterol biosynthesis pathway, which also serves as a precursor pathway for CoQ10 biosynthesis. By inhibiting the conversion of squalene, terbinafine reduces the availability of crucial substrates for COQ10B, leading to its functional inhibition.