ACOT3 Activators

Chemical activators of acyl-CoA thioesterase 3 encompass a variety of CoA derivatives that engage with the enzyme to initiate its hydrolytic activity. Palmitoyl-CoA, oleoyl-CoA, stearoyl-CoA, myristoyl-CoA, arachidonoyl-CoA, linoleoyl-CoA, acetyl-CoA, butyryl-CoA, propionyl-CoA, dodecanoyl-CoA, and malonyl-CoA are all substrates for acyl-CoA thioesterase 3, each activating the enzyme by serving as specific reactants that are transformed during the enzymatic process. For instance, palmitoyl-CoA, when hydrolyzed by acyl-CoA thioesterase 3, leads to the liberation of both CoA and palmitic acid, a saturated fatty acid. Similarly, oleoyl-CoA and linoleoyl-CoA, both of which are unsaturated fatty acid CoA derivatives, are also substrates for the enzyme. Their hydrolysis by acyl-CoA thioesterase 3 results in the release of free oleic and linoleic acids, respectively, along with CoA.

In addition to fatty acid CoA derivatives, acyl-CoA thioesterase 3 can also act upon shorter chain acyl-CoAs, such as acetyl-CoA and butyryl-CoA, triggering the release of their corresponding acids-acetic and butyric-and CoA. Propionyl-CoA, upon hydrolysis, yields propionic acid and CoA, further illustrating the enzyme's broad substrate specificity. Dodecanoyl-CoA and malonyl-CoA are also included in this spectrum of activators, albeit malonyl-CoA is a less typical substrate, it too is hydrolyzed by the enzyme, producing malonic acid and CoA. Acyl-CoA thioesterase 3's activity is not directly stimulated by α-ketoglutarate, but its role in metabolic pathways can enhance the pool of available CoA derivatives, thus indirectly promoting the enzyme's functional potential. This diverse array of activators demonstrates the enzyme's capacity to interact with different substrates, initiating its hydrolytic action to regulate the intracellular levels of both acyl-CoAs and free fatty acids.