The Role of Glyoxalase in Glycation and 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 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. Further, glycation of nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and methylglyoxal (MGO), cause 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 antiglycation defense is well established. Glycation of proteins by MGO and GO results in protein misfolding, thereby affecting their structure and function. These findings provide the evidence for the rationale that the functional modulation of GLO pathway could be used as a potential therapeutic target. In the present review, we summarize the newly emerged literature on GLO pathway including enzymes regulating the process. In addition, we describe 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.

Association of Novel Advanced Glycation End-Product (AGE10) with Complications of Diabetes as Measured by Enzyme-Linked Immunosorbent Assay

“…Non-enzymatic modification of macromolecules by sugars is a main culprit in the pathogenesis of diabetic complications [ 28 , 29 , 30 ] and the resulting products may serve as biomarkers of metabolic disorders and treatment efficacy. Currently, fructosyllysine, glycated albumin (GA) and glycated hemoglobin (HbA1c) are used in clinical practice.…”

Nephroprotective effects of polyherbal extract via attenuation of the severity of kidney dysfunction and oxidative damage in the diabetic experimental model

“…Studies in patients with type 2 diabetes mellitus indicate that while poor metabolic control is the most important determinant of the development of nephropathy, hyperlipidemia and hypertension are equally responsible for this condition (4). DN is characterized by a change in functional as well as structural integrity, which causes intraglomerular hypertension leading to further deterioration of the kidney and consequently resulting in end-stage renal disease (5)(6)(7). Structural and functional changes occur at glomeruli and tubular level and are marked as a glomerular epithelial cell (podocyte) loss, renal hypertrophy, mesangial expansion, expansion of tubular basement membranes, tubular atrophy, and glomerular basement membrane thickening and fibrosis due to excessive accumulation of extracellular matrix (ECM) proteins (8).…”

Screening of the antioxidant and antibacterial effects of extracted essential oils from Thunbergia coccinea, Acacia polyacantha, Polygonum micrpcephallum, Abies spectabilis and Clerodendrum colebrookianum

“…It has been seen that the majority of wild comestible plant products have a therapeutic property and can be utilized to heal customary afflictions; these are effortlessly accessible; inexpensive and also outstanding originators of nutrients like essential minerals; proteins; iron; other secondary metabolites and carbohydrates. Systematic utilization of these plant products produces an unconventional origin of medicines (6,7). Therapeutic plants depict a limitless provenance of -saving medicines for most of the world's population (8).…”