Phthalate monoesters, the endocrine-active primary metabolites of phthalate diesters found in a variety of common products, affect reproductive development in male fetuses. Lipases convert phthalate diesters into monoesters during Phase I metabolism. During Phase II, phthalate monoesters further biotransform using UDP-glucuronosyltransferase enzymes (UGTs) and are excreted in urine, eliminating their toxic potential. Data suggest a significant minority of people glucuronidate poorly, leaving them more susceptible to the effects of phthalate diesters, as well as conditions like Gilbert’s syndrome and Crigler-Najjar syndrome. Little data exists on the enzymatic kinetics of UGTs on most phthalate monoester substrates, so the goal of the present study is to determine the kinetic relationship between three UGT isoforms UGT1A3, UGT1A8, and UGT2B7; and three phthalate monoester substrates mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), and mono-n-octyl phthalate (MNOP). Previous research suggests that these isoforms fit the Michaelis-Menten model on MEHP substrates, so the selected isoforms will be tested to see if they show similar kinetic behavior when metabolizing other long chain phthalate monoesters to provide a deeper understanding of the glucuronidation of phthalate monoesters. In addition, using a dataset from a previous study, we will examine the relationship between the ratio of conjugated to unconjugated phthalate monoester and total monoester concentration in a single human subject to better understand factors that relate to lower levels of UGT expression in an individual.
