Page 206 - The Toxicology of Fishes

186 The Toxicology of Fishes

Exon 1ʼs
Common
exons

ZF5

ZF7

ZF6

FIGURE 4.9 Structure of the zebrafish UGT1B gene showing alternative splicing of primary transcripts.

HO
O
H O
UGT H
O
HO
OH HO H OH
OH H OH H
FIGURE 4.10 Glucuronidation of benzo(a)pyrene-7,8-dihydrodiol catalyzed by UGT.

case of fish, excretion of glucuronides of sex steroids as pheromones and spawning stimulants (Lambert
and Resink, 1991). Many of the enzymes have a broad and overlapping substrate specificity, which gives
them the ability to conjugate many xenobiotic compounds in addition to their preferred endobiotic
substrates. This appears to be the case for those conjugating bilirubin and planar polyaromatic phenols,
although several isoenzymes, particularly those metabolizing steroid hormones, appear to show a more
restricted substrate specificity (Table 4.7).
Most investigations of fish have been in vivo studies concerned with the identification of the glucu-
ronides of endobiotic and xenobiotic compounds. Glucuronide conjugates of bilirubin, 17β-estradiol,
triiodothyronine (T ), and thyroxine (T ) have been identified in the bile of several fish species, whereas
4
3
glucuronides of 3α-, 3β-, and 17β-hydroxy steroids and their metabolites have been identified in several
tissues and body fluids, showing that the scope for endogenous compounds is the same as in mammals
(George, 1994).
Quantitatively, glucuronidation is the most important pathway for detoxication and excretion of
xenobiotic compounds in mammals, and studies to date indicate that this is also the case in fish. A recent
listing of the wide and structurally diverse range of xenobiotic compounds whose glucuronides have
been detected in bile, urine, and various tissues is given in Table 4.8. Compared with the large number
of compounds shown to be glucuronidated in vivo, few studies have been reported on the scope of

TABLE 4.7
Substrate Specificities of Some Mammalian UGT Isoenzymes and
Some Xenobiotics Conjugated
Endogenous Substrates Xenobiotic Substrates
Bilirubin, thyroxine, 5-OH tryptamine 4-Nitrophenol (4NP)
Retinol (?) 1-Naphthol (1-NA)
Testosterone (17β-OH steroid) 4-Methyl umbelliferone
Androsterone (3α-OH steroid), lithochlolate 4-Aminobiphenyl
Estrone, 2-estradiol
Olfactory stimulants