Title:The Role of Glyoxalase in Glycation and Carbonyl Stress Induced Metabolic Disorders
Volume: 21
Issue: 9
Author(s): Mohd Saeed*, Mohd Adnan Kausar*, Rajeev Singh, Arif J. Siddiqui and Asma Akhter
Affiliation:
- Department of Biology, College of Sciences, University of Hail, Hail,Saudi Arabia
- Department of Biochemistry, College of Medicine, University of Hail, Hail,Saudi Arabia
Keywords:
GLO, MGO, GO, advanced glycation end products (AGEs), metabolic pathway, carbonyl stress induced metabolic
disorders.
Abstract: Glycation refers to the covalent binding of sugar molecules to macromolecules, such as
DNA, proteins, and lipids in a non-enzymatic reaction, resulting in the formation of irreversibly bound
products known as advanced glycation end products (AGEs). AGEs are synthesized in high amounts
both in pathological conditions, such as diabetes and under physiological conditions resulting in aging.
The body’s anti-glycation defense mechanisms play a critical role in removing glycated products.
However, if this defense system fails, AGEs start accumulating, which results in pathological conditions.
Studies have been shown that increased accumulation of AGEs acts as key mediators in multiple
diseases, such as diabetes, obesity, arthritis, cancer, atherosclerosis, decreased skin elasticity, male
erectile dysfunction, pulmonary fibrosis, aging, and Alzheimer’s disease. Furthermore, glycation of
nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and
methylglyoxal (MGO), causes potential damage to the genome, proteome, and lipidome. Glyoxalase-1
(GLO-1) acts as a part of the anti-glycation defense system by carrying out detoxification of GO and
MGO. It has been demonstrated that GLO-1 protects dicarbonyl modifications of the proteome and
lipidome, thereby impeding the cell signaling and affecting age-related diseases. Its relationship with
detoxification and anti-glycation defense is well established. Glycation of proteins by MGO and GO
results in protein misfolding, thereby affecting their structure and function. These findings provide
evidence for the rationale that the functional modulation of the GLO pathway could be used as a potential
therapeutic target. In the present review, we summarized the newly emerged literature on the GLO
pathway, including enzymes regulating the process. In addition, we described small bioactive molecules
with the potential to modulate the GLO pathway, thereby providing a basis for the development
of new treatment strategies against age-related complications.
