Lactoylglutathione lyase

lactoylglutathione lyase
Ribbon diagram of human glyoxalase I with its catalytic zinc ions shown as two purple spheres. An inhibitor, S-hexylglutathione, is shown as a space-filling model; the green, red, blue and yellow spheres correspond to carbon, oxygen, nitrogen and sulfur atoms, respectively.
Identifiers
EC number	4.4.1.5
CAS number	9033-12-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

GLO1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BH5, 1FRO, 1QIN, 1QIP, 3VW9, 3W0T, 3W0U
Identifiers
Aliases	GLO1, GLOD1, GLYI, HEL-S-74, glyoxalase I
External IDs	MGI: 95742 HomoloGene: 4880 GeneCards: GLO1
Gene ontology Molecular function • lactoylglutathione lyase activity • zinc ion binding • metal ion binding • lyase activity Cellular component • cytoplasm • extracellular exosome • nucleus • cytosol • plasma membrane Biological process • regulation of transcription from RNA polymerase II promoter • osteoclast differentiation • negative regulation of apoptotic process • methylglyoxal metabolic process • glutathione metabolic process • pyruvate metabolic process • carbohydrate metabolic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2739	109801
Ensembl	ENSG00000124767	ENSMUSG00000024026
UniProt	Q04760	Q9CPU0
RefSeq (mRNA)	NM_006708	NM_001113560 NM_025374
RefSeq (protein)	NP_006699	NP_001107032.1 NP_079650.3 NP_001107032 NP_079650
Location (UCSC)	Chr 6: 38.68 – 38.7 Mb	Chr 17: 30.59 – 30.61 Mb
PubMed search

In enzymology, a lactoylglutathione lyase (EC 4.4.1.5) (also known as glyoxalase I) 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.

Glyoxalase I derives its name from its catalysis of the first step in the glyoxalase system, a critical two-step detoxification system for methylglyoxal. Methylglyoxal is produced naturally as a byproduct of normal biochemistry, but is highly toxic, due to its chemical reactions with proteins, nucleic acids, and other cellular components. The second detoxification step, in which (R)-S-lactoylglutathione is split into glutathione and D-lactate, is carried out by glyoxalase II, a hydrolase. Unusually, these reactions carried out by the glyoxalase system does not oxidize glutathione, which usually acts as a redox coenzyme. Although aldose reductase can also detoxify methylgloxal, the glyoxalase system is more efficient and seems to be the most important of these pathways. Glyoxalase I is an attractive target for the development of drugs to treat infections by some parasitic protozoa, and cancer. Several inhibitors of glyoxalase I have been identified, such as S-(N-hydroxy-N-methylcarbamoyl)glutathione.

Glyoxalase I is classified as a carbon-sulfur lyase although, strictly speaking, the enzyme does not form or break a carbon-sulfur bond. Rather, the enzyme shifts two hydrogen atoms from one carbon atom of the methylglyoxal to the adjacent carbon atom. In effect, the reaction is an intramolecular redox reaction; one carbon is oxidized whereas the other is reduced. The mechanism proceeds by subtracting and then adding protons, forming an enediolate intermediate, rather than by transferring hydrides. Unusually for a metalloprotein, this enzyme shows activity with several different metals. Glyoxalase I is also unusual in that it is stereospecific in the second half of its mechanism, but not in the first half. Structurally, the enzyme is a domain-swapped dimer in many species, although the two subunits have merged into a monomer in yeast, through gene duplication.