Mechanisms of Drug Metabolism

Abstract

The study of drug metabolism places significant importance on the molecular properties of the substrate and the topography of the enzyme's active site. Mechanisms of drug metabolism focus on the different reactions catalyzed within each family of drug‐metabolizing enzymes as well as the chemistry involved in phase I and II reactions. Concepts explored include enzyme‐catalyzed reaction mechanisms, physicochemical properties of substrate molecules that result in favorable sites of metabolism for a given enzyme, and factors that contribute to the regioselectivity and stereoselectivity observed for phase I and II drug‐metabolizing enzymes.

Cytochrome P450 and Other Drug-Metabolizing Enzymes As Therapeutic Targets

“…Toward the possibility of utilizing UGTs as a therapeutic target, recent research has begun to focus on the role that UGTs play in the regulation of endogenous molecules involved in tumorigenesis and progression (Allain et al, 2020a). In a similar vein, SULTs increase the hydrophilicity of their target molecules by catalyzing the transfer of a sulfonyl moiety from PAPS (3phosphoadenosine-5-phosphosulfate) to a nucleophilic functional group, many of which are the same as those noted above for UGTs (Foti et al, 2012). SULTs are divided into membrane-bound and cytosolic groupings, with the metabolism of xenobiotics generally attributed to the latter (Gamage et al, 2006).…”

“…The With regard to studying the role of drug metabolizing enzymes in the regulation of disease mechanisms and the subsequent potential to utilize them in therapeutic regimens, the glutathione Stransferase (GST) enzymes have also received a significant amount of attention to date. GSTs (both membrane-bound and cytosolic) catalyze the addition of glutathione (GSH) to an electrophilic substrate, resulting in a key detoxification and elimination mechanism for a multitude of substrates (Foti et al, 2012). Well-studied GST substrates include aflatoxin B1, cisplatin, acrolein and 4hydroxynonenal (Allocati et al, 2018).…”