Page 205 - The Toxicology of Fishes

Biotransformation in Fishes 185

0.05
HS1A1
HS1A4 1A family, alternatively
HS1A3 spliced 5-exon gene
HS1A5
“bilirubin” cluster
HS1A6
“phenol” cluster
HS1A10
HS1A8 planar aromatic
HS1A7 nonplanar aromatic
HS1A9
5248/27733[ZF4]
5248/24535
6220/AI558859[ZF5] 1B Family,
(ZF5, 6, 7 alternatively
6220/19395[ZF6]
spliced 5-exon gene)
6220/26608[ZF7]
PLAICEugt1b1
FLOUNDER
11537/22219
2 (C) Family,
22219/BM104511
6-exon genes
4649/28543[ZF8]
(8, 9, 10 alternatively
4649/38031[ZF10] spliced)
4649/15212[ZF11]
HS2A1
HS2B4 2A Olfactory
HS2B10
HS2B11 2B Steroid/bile acid,
HS2B15 6-exon genes
HS2B17
16479/25419[ZF1]
10416B/9895.2 3 Family,
6372/22035[ZF2] single-exon genes
14647/25303 (unique to fish)
NA14673/BF717778
PlaiceGSTA
FIGURE 4.8 Phylogenetic relationships of expressed fish and human (HS) UGTs. The zebrafish protein sequences were
translated from the genome sequence for which there are reported EST data (gene/protein numbers given [ZF]). (From
George, S.G. and Taylor, A., Mar. Environ. Res., 54, 253, 2002. With permission.)

Reactions and Substrate Specificity
The spectrum of the acceptor substrates is very wide and, as with most enzymes that exhibit a broad
specificity for structurally diverse compounds, multiple isoenzymes belonging to a number of multigene
families are found (Mackenzie et al., 1997). The enzymes catalyze the transfer (conjugation) of glucuronic
acid from the high-energy nucleotide UDP-glucuronic acid (UDPGA) to a wide variety of acceptor
substrates (aglycones) to form β-glucuronides (Figure 4.10). The most common are the formation of
O-glucuronides from alcohols, phenols, and carboxylic acids and N-glucuronides of carbamates, amides,
and amines. S-Glucuronides of aryl mercaptans and thiocarbamates and C-glucuronides formed by
conjugation of 1,3-dicarbonyls have also been identified in mammals but not so far in aquatic species.
The endogenous roles of these enzymes are in the detoxification of toxic metabolites (e.g., bilirubin)
formed from the degradation of heme, the secretion of bile acids (e.g., lithocholate), termination of
hormone action (retinol, T , T , sex steroids), cessation of the action of olfactory stimulants, and, in the
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