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Glucuronidation in the polar bear (Ursus maritimus)
James C Sacco1, Margaret O James
1Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, 1600 S.W. Archer Road, Room P6-20, Gainesville, FL 32610-0485, USA.
Marine Environmental Research
|June 5, 2004
Summary
Polar bears possess UDP-glucuronosyltransferase (UGT) enzymes in their liver, crucial for metabolizing hydroxylated polychlorinated biphenyls (OH-PCBs) and other pollutants. This study quantifies UGT activity, revealing significant potential for detoxification in these Arctic apex predators.
Area of Science:
- Environmental Toxicology
- Biochemistry
- Arctic Wildlife Biology
Background:
- Polar bears accumulate lipophilic pollutants like polychlorinated biphenyls (PCBs) from their marine diet.
- Hydroxylated PCB metabolites (OH-PCBs) are found in polar bear plasma, indicating liver biotransformation.
- Phase 2 metabolism of hydroxylated xenobiotics in polar bears remains poorly understood.
Purpose of the Study:
- To investigate UDP-glucuronosyltransferase (UGT) activity in polar bear liver.
- To assess UGT activity using hydroxylated PCBs (OH-PCBs) and 3-hydroxy-benzo(a)pyrene (3-OH-BaP) as substrates.
- To characterize the kinetic parameters of UGT activity for these xenobiotics.
Main Methods:
- Preparation of liver microsomes from frozen polar bear samples.
- Enzymatic assays using fluorescence and radiolabeled substrates ([14-C]-UDPGA) to measure UGT activity.
- Kinetic analysis (Km, Vmax) of UGT activity with 3-OH-BaP, 4'-OH-CB72, and 4'-OH-CB159.
Main Results:
- Polar bear liver microsomes exhibited measurable UGT activity with 3-OH-BaP (Km 1.71 µM, Vmax 1.26 nmol/min/mg).
- Significant glucuronidation of model OH-PCBs was observed, with higher efficiency for 4'-OH-CB72 (Km 7.3 µM, Vmax 1.55 nmol/min/mg) than 4'-OH-CB159 (Km 16.1 µM, Vmax 0.46 nmol/min/mg).
- Spontaneous glucuronide formation from endogenous substrates or contaminants was noted in polar bear microsomes.
Conclusions:
- Polar bear liver possesses active UGT enzymes capable of metabolizing hydroxylated persistent organic pollutants.
- The findings suggest a functional detoxification pathway for OH-PCBs and related compounds in polar bears.
- Further research is needed to identify the specific aglycones contributing to glucuronidation in vivo.