Albumin stimulates the activity of the human UDP-glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the effects are enzyme and substrate dependent

PLoS One. 2013;8(1):e54767. doi: 10.1371/journal.pone.0054767. Epub 2013 Jan 23.


Human UDP-glucuronosyltransferases (UGTs) are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA) significantly enhances in vitro activities of UGTs, a limiting factor in in vitro-in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2-4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction's K(m), increasing its V(max), or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions' K(m) are concerned. In the cases of V(max) values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to V(max) increases. Additionally, the BSA effects may be UGT subfamily dependent since K(m) decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large V(max) increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Enzyme Activation / drug effects
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Kinetics
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Serum Albumin, Bovine / pharmacology*
  • Substrate Specificity


  • Isoenzymes
  • Recombinant Fusion Proteins
  • Serum Albumin, Bovine
  • bilirubin uridine-diphosphoglucuronosyl transferase 1A10
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 2B15, human
  • UDP-glucuronosyltransferase, UGT1A7
  • UDP-glucuronosyltransferase, UGT1A8
  • UGT2A1 protein, human

Grants and funding

This study was supported by the Sigrid Juselius Foundation, the Graduate School in Pharmaceutical Research, the Academy of Finland (project numbers 120975 and 1260010), the University of Helsinki Research Foundation grant for young researchers, and the European Erasmus programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.