About Glyoxalase-1 / GLO1:
Glyoxalase I, which is also known as GLO1, is a type of protein that binds glutathione and is involved in detoxifying methylglyoxal. Methylglyoxal is a byproduct of glycolysis. Glyoxalase II and GLO1 catalyse successive steps in the pathway. Below, we will provide you with a better understanding of GLO1. This includes explaining what the glyoxalase system is, as well as looking at the gene structure of GLO1 and how this protein relates to disease.
The glyoxalase system is a number of different enzymes that have the purpose of carrying out methylglyoxal detoxification, as well as the other reactive aldehydes that are created as part of our metabolism’s normal function. This system has been studied in both eukaryotes and bacteria.
The detoxification process takes place by two thiol-dependent enzymes in sequential action. The first is GLO1. this catalyzes the isomerization of the hemithioacetal adduct that is formed spontaneously between 2-oxoaldehydes and GSH into S-2-hydroxyacylglutathione. The second is when the thiolesters are hydrolyzed by glyoxalase II. When it comes to methylglyoxal catabolism, S-D-lactoyl-glutathione produces both GSH and D-lactate.
There are a lot of typical features of the enzymes that dispose of endogenous toxins found within this system. For example, first and foremost, a narrow substrate specificity is shown. This is in incredible contrast to the spectrum of a lot of the enzymes that are involved in xenobiotic metabolism. A second example of this is when the enzymatic mechanism requires intracellular thiols. And thirdly, reactive metabolites are recycled by the system back to form, and this could be helpful when it comes to cellular metabolism.
Glyoxalase I is a putative drug target for trypanosomatids. Trypanosomatids are pathogenic protozoa, which includes leishmaniasis’ causative agents. Human myeloid leukemia cells will become resistant to doxorubicin (DOX) treatment. This resistance is linked with a heightened glyoxalase 1 expression. When treated with BBGC, human lung cancer DMS114 cells and NCI-H522 cells, which express higher GLO1 activity, underwent apoptosis. However, this did not happen with A549 cells, which express lower activity.