Physiological metabolic enzymes and transporters (DMETs)

Physiological metabolic enzymes and transporters (DMETs) represent a broad and diverse category of proteins responsible for the absorption, distribution, metabolism, and excretion (ADME) of both endogenous metabolites and exogenous compounds, such as drugs and toxins. This group primarily includes Phase I enzymes like the Cytochrome P450 (CYP) family, Phase II conjugating enzymes such as UDP-glucuronosyltransferases (UGTs), and various membrane transporters from the Solute Carrier (SLC) and ATP-Binding Cassette (ABC) superfamilies (Zanger & Schwab, 2013; Giacomini et al., 2010). These proteins are essential for maintaining metabolic homeostasis and facilitating detoxification by converting lipophilic substances into polar, excretable forms. While they are rarely the primary therapeutic targets for treating a specific disease, they are critical determinants of a drug's pharmacokinetic profile and systemic exposure (FDA, 2020). Genetic polymorphisms in these enzymes and transporters, along with drug-induced inhibition or induction, are the primary drivers of inter-individual variability in drug response and the occurrence of clinically significant drug-drug interactions. Consequently, evaluating a drug's interaction with these physiological systems is a mandatory component of the drug development and regulatory approval process to ensure patient safety and therapeutic efficacy (PharmGKB, 2023).

Other names

Drug-metabolizing enzymes and transportersADME proteinsXenobiotic-metabolizing enzymesDrug disposition proteins

Drugs interact with these proteins as substrates, inhibitors, or inducers, thereby modulating the rate of metabolism and transport of co-administered medications.