Glyoxalase system
Encyclopedia
The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal
and the other reactive aldehyde
s that are produced as a normal part of metabolism
. This system has been studied in both bacteria
and eukaryote
s.
This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І
, which catalyses the isomerisation of the spontaneously formed hemithioacetal adduct between GSH and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione. Secondly, glyoxalase ІІ
hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione.
This system shows many of the typical features of the enzymes that dispose of endogenous toxins. Firstly, in contrast to the amazing substrate range of many of the enzymes involved in xenobiotic metabolism
, it shows a narrow substrate specificity. Secondly, intracellular thiol
s are required as part of its enzymatic mechanism and thirdly, the system acts to recycle reactive metabolites back to a form which may be useful to cellular metabolism.
Methylglyoxal
Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal is the aldehyde form of pyruvic acid. It has two carbonyl groups, so it is a dicarbonyl compound. Methylglyoxal is both an aldehyde and a ketone....
and the other reactive aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s that are produced as a normal part of metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. This system has been studied in both bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s.
This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І
Lactoylglutathione lyase
In enzymology, a lactoylglutathione lyase is an enzyme that catalyzes the isomerization of hemithioacetal adducts, which are formed in a spontaneous reaction between a glutathionyl group and aldehydes such as methylglyoxal.The systematic name of this enzyme class is -S-lactoylglutathione...
, which catalyses the isomerisation of the spontaneously formed hemithioacetal adduct between GSH and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione. Secondly, glyoxalase ІІ
Hydroxyacylglutathione hydrolase
In enzymology, a Hydroxyacylglutathione hydrolase is an enzyme that catalyzes the chemical reactionHence, this enzyme has two substrate, -S-lactoylglutathione and water, and two products, glutathione and a 2-hydroxy carboxylate...
hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione.
This system shows many of the typical features of the enzymes that dispose of endogenous toxins. Firstly, in contrast to the amazing substrate range of many of the enzymes involved in xenobiotic metabolism
Xenobiotic metabolism
Xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons...
, it shows a narrow substrate specificity. Secondly, intracellular thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
s are required as part of its enzymatic mechanism and thirdly, the system acts to recycle reactive metabolites back to a form which may be useful to cellular metabolism.