Epoxide Hydrolases

Epoxides are harmful cyclic ethers produced or introduced in biological system.

Epoxide Hydrolase (EH) is gene family present in all domains of life, which catalyses the hydration reaction of epoxides and turns the toxic epoxides into compounds less toxic, more soluble and easier to eliminate.

In mammals, EH genes are classified into five subfamilies: microsomal cholesterol 5,6-oxide hydrolase, hepoxilin A3 hydrolase, leukotriene A4 hydrolase, soluble epoxide hydrolase (sEH), and microsomal epoxide hydrolase (mEH). Two of those have toxicological relevance: the mEH and the sEH. The mEH is the principal enzyme in the metabolism of epoxides xenobiotics. The N-terminal region of this proteins is transmembranal, and the catalytic site is located at the C-terminal. The sEH has a complementar function in the metabolism of epoxides xenobiotics, and both N-terminal and C-terminal are catalytic sites.

For more information about the EH, please refer to the great paper from Fretland et al. 2000, entitled "Epoxide hydrolases: biochemistry and molecular biology" and published at Chemico-Biological Interactions 129, 41–59.

In the 16 transcriptomes we have sequenced, 186 EH were found. Of those, 108 sequences are from soluble EH and 78 from microssomal EH. There are 55 sequences with <75% of the coding sequence (CDS); 36 mEH and 18 from sEH. We are currently looking for evidences of episodic diversifying selection in those sequences and exposing selected species to evaluate the regulation of loricariids EH to xenobiotics.

Chemistry Nobel Honors 2015

Have you heard about the 2015 Nobel prizes in Chemistry?

For their work on the mechanisms of DNA repair three scientists were awarded, namely: Paul Modrich, from the Howard Hughes Medical Institute and Duke University School of Medicine; Aziz Sancar, from the University of North Carolina; and Tomas Lindahl, from the Francis Crick Institute and the Clare Hall Laboratory won for their studies about DNA's repair mechanisms.

The DNA molecule can be altered or damaged by radiation, sunlight, toxic man-made or natural chemicals compounds. In fact, normal reactions inside the cell produce reactive oxygen species capable to damage the DNA. Moreover, when the cell is copying its DNA, errors happen at a constant rate. If these errors are not removed, they become fixed and can cause diseases. In order to cope with all these sources of DNA damage, cells have evolved complex defence mechanisms, including to repair DNA lesions.

Thomas Lindahl discovered the base excision repair (BER) mechanism in 1970, that occurs when a base of a nucleotide is damaged and this mechanism doesn't allow a mutation is determined in our DNA. .

Paul Modrich discovered the cellular mismatch repair mechanism in cells. When DNA is copied during cell division, mismatch nucleotides can be incorporated into the new strand and it is problematic. So, the cellular mismatch repair mechanism detects and eliminates errors, allowing you to make a correct copy of DNA and helps avoid complicated mutations.

And Aziz Sancar contributed discovering the nucleotide excision repair (NER) mechanism that removes DNA damage induced by ultraviolet light. When the error is  acknowledged the entire nucleotide is removed, not just the base.