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Phylogenetic Origins for Differences in Detoxification Enzymes in Marine Fish and Other Vertebrates

Peter van den Hurk, Clemson University, Department of Biological Sciences

26 October 2018

Over the last decades, several examples have been discovered of perplexing differences in the expression of phase 2 detoxification enzymes in vertebrate species. These enzymes, also known as drug-metabolizing enzymes, comprise groups as the sulfotransferases, UDP-glucuronosyltransferases, and glutathione S-transferases. They are involved in conjugating a hydrophilic group to a poorly water soluble substrate, thus reducing the toxicity of the substrate, and facilitating the excretion of the conjugated complex. To further investigate species differences in fish taxa, a variety of species was evaluated for the activity of sulfation and glucuronidation enzymes, using 17B-estradiol and 9-hydroxy-benzo[a]pyrene as substrates. Primitive fish species like hagfish and lamprey appeared to have no glucuronidation activity towards these substrates, while activity in sharks and rays was much lower than in bony fishes. This indicates that the earliest vertebrates had no glucuronidation capacity, and that the array of glucuronosyltransferases that is known in more modern fish species and other vertebrates has evolved later. However, there are dramatic examples of other vertebrates that don't have glucuronidation activity towards phenolic substrates. The van den Hurk lab demonstrated that a number of snake species also lack glucuronidation activity; while other reptilians (turtles, alligators) had much lower activity than mammals. But even among the mammals it is known that felines lack phenol-type glucuronidation activity, which makes them extremely sensitive to compounds like acetaminophen. This diverse expression of glucuronosyltransferases in different vertebrate taxa is probably a combination of phylogenetic origins and the degradation of genomic information in genes that are not essential in apex carnivores like cats and snakes.