Phylogenetic patterns of phase II biotransformation enzymes in lower vertebrates

Over the last decades, more and more examples have been discovered of unexpected differences in the expression of phase 2 detoxification enzymes in vertebrate species, not only in UDP-glucuronosyltransferases but also in sulfotransferases. These enzymes are involved in metabolizing poorly water-soluble substrates, facilitating the excretion of the toxicant. To further investigate species differences in marine fish taxa, a variety of species was evaluated for the activity of sulfation and glucuronidation enzymes. Primitive fish species like hagfish and lamprey appeared to have no glucuronidation activity towards phenolic substrates, while activity in sharks and rays was much lower than in bony fishes. This would indicate 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 examples of other vertebrates that also don't have glucuronidation capability towards phenolic substrates. We performed experiments to demonstrate that snake species lack phenol-type glucuronidation activity compared to other reptilians. This makes certain chemicals extremely toxic for snakes, and is used for management of invasive snake species, like the brown treesnake on Guam. In addition, even among the mammals it has been known that felines lack phenol-type glucuronidation activity, which makes them extremely sensitive to compounds like acetaminophen. Our latest research showed that also among bird species a large variety in glucuronosyltransferase enzymes is found. The explanation for 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 obligate carnivores like cats, snakes and birds of prey. This differentiated expression of glucuronosyltransferases can explain observed differences in sensitivity towards phenol-type pollutants in environmentally relevant species.

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