Effects of uridine diphosphate glucuronosyltransferase activity on the maximal secretion rate of bilirubin conjugates in the rat

摘要: Abstract It is generally accepted that biliary secretion rate-limiting for the plasma-to-bile transport of a saturating load bilirubin. Previous studies from this laboratory have suggested relationship between hepatic bilirubin uridine diphosphate glucuronosyltransferase activity and apparent maximal rate (excretory maximum). The present study was undertaken to further investigate in rats with wide range transferase levels analyze effects on formation monoglucuronides diglucuronides vivo vitro. Animals moderately decreased enzyme still showed near-normal excretory maximum but fractional amounts conjugated bilirubine plasma liver ratio diconjugates monoconjugates bile, liver, plasma. A more pronounced decrease level yielded lower values as well. Enhanced activities were obtained by pretreatment series enzyme-inducing agents, usually at dosages not influencing bile flow. An enhanced produced significant increases maximum, concentrations both unconjugated bilirubins plasma, an increased liver. In all animals, observed correlated found after incubation homogenates vitro low substrate. Overall, can best be described hyperbolic curve. At "saturation" values, no increase conjugates or could observed, suggesting secretion, per se, rather conjugation rate-limiting. latter seems than assayed activity. investigations point equilibration pigments bile. estimated assay (but high activities) determines rate, three compartments studied, relative amount Our suggest secretory step major determinant rate.