This understanding first came about when it was seen that people suffering from Gilbert syndrome (a genetic impairment of the UDPGT
enzyme that reduces rates of conjugation of bilirubin) have far lower rates of cardiovascular disease than the general population.
A liver sample from the first five animals of each dose group was processed to measure 5'-deiodinase I (5'-DI) and uridine diphosphate-glucuronyltransferase (UDPGT) activity.
The microsomal pellets were resuspended in the homogenization buffer at a protein concentration of 10-20 mg/mL, aliquoted, and stored between -65[degrees]C and -85[degrees]C until analyzed for UDPGT and 5'-DI.
The other is an olfactory-specific form of a different class of detoxification enzymes, known as the uridine diphosphate glucuronyl transferases, or UDPGTs
. These typically pick up where a cytochrome P450 leaves off, transforming a water-avoiding molecule into a water-loving form readily cleared from tissue.
In addition, hexachlorobenzene increased the activity of hepatic [T.sub.4] UDPGT in a time-dependent manner without changes in [T.sub.3]-UDPGT (Alvarez et al.
Mercury-induced UDP-glucuronyltransferase (UDPGT) activity in mouse kidney Toxicology 64:81-87.
G as the proportion of the general population with the Gilbert genotype, that is, the proportion of the population who are homozygous for the proposed UDPGT promoter insertion mutation;
We assume that Gilbert's is recessive for the alteration in the promoter sequence for UDPGT. Our findings would be equally relevant if the abnormal genotype were dominant, with the heterozygous state able to cause symptoms.
Anti-microsomal antibodies targeting P450IA2 and P450IIIAl isoenzymes have also been reported in idiosyncratic liver injuries associated with dihydralazine and aromatic anticonvulsants, as well as anti-LKM3 antibodies directed against uridine diphosphate glucuronyltransferase (UDPGT) enzymes [24-26].
The most common type of phase II reaction is glucuronidation, where glucuronic acid is transferred from uridine diphosphate glucuronic acid (UDPGA) to a drug or phase I metabolite by the enzyme UDPGT .
This was accompanied by decreases in [T.sub.4] and [T.sub.3] and an increase in TSH, as well as effects on the liver, including increases in liver weight and EROD, pentoxyresorufin O-deethylase (PROD), and UDP-glucuronosyltransferase (UDPGT) activity at doses of 30 and 60 mg/kg (Stoker et al.
The decrease in [T.sub.4] was associated with an induction of UDPGT, the key phase II metabolizing enzyme involved in the conjugation of [T.sub.4].