What are the Real Causes of Substrate Inhibition in the Glucuronidation Reaction?

UDP-Glucuronosyltransferases (UGTs) are a class of enzymes (please refer to Mackenzie et al. [1] for UGT nomenclature and classification) anchored in the membrane of endoplasmic reticulum. The UGT enzyme catalyzes glucuronidation, a major metabolic pathway in humans, by transferring a glucuronic acid from the cofactor UDPglucuronic acid to the substrate. In vitro characterization has revealed that many human UGT enzymes display substrate inhibition kinetics (i.e., inhibition of enzyme activity at high substrate concentrations) [2]. It is interesting to note that plant UDP-glucosyltransferases (using a similar catalytic mechanism as human UGTs), which are water-soluble, also display substrate inhibition kinetics. For example, plant UGT73C8 and UGT88E1 from Medicago truncatula [3], and UGT78K1 from black soybean (with cyanidin as the substrate) [4].