Methylglyoxal, or MGO, is a reactive organic compound that forms naturally within the human body as a byproduct of normal metabolism. While it is a normal occurrence, its accumulation can become problematic. This compound is also present in various foods and beverages.
Formation and Sources of Methylglyoxal
Methylglyoxal originates from both internal (endogenous) and external (exogenous) sources. The primary internal pathway for its formation is as a side-product of glycolysis, the metabolic process that breaks down glucose for energy. While glycolysis is the main source, MGO can also arise from the metabolism of certain amino acids and fats.
The compound is also ingested through dietary sources, commonly in foods and beverages that have undergone heat treatment or fermentation. Items like coffee, caramel, and bread crust contain MGO from the chemical reactions during roasting and baking. Many processed foods also contribute to dietary intake.
A notable dietary source is Manuka honey from New Zealand’s MÄnuka tree. Its high MGO content results not from heating but from the natural conversion of dihydroxyacetone (DHA), a compound in the flower’s nectar. As the honey ripens, DHA is transformed into MGO, leading to the high concentrations that characterize this honey.
Cellular Effects of Methylglyoxal
Methylglyoxal’s high reactivity dictates its effects at a cellular level, as it readily binds to macromolecules such as proteins, lipids, and nucleic acids like DNA. This binding process results in the formation of complex structures known as Advanced Glycation End-products, or AGEs.
AGEs are modified molecules that can no longer perform their intended biological functions correctly. When proteins are modified by MGO, their structure can be altered, impairing their enzymatic activity or role in cellular signaling and structure. The accumulation of these non-functional AGEs disrupts normal cellular operations.
The reactions of MGO also contribute to increased oxidative stress, an imbalance between reactive oxygen species (free radicals) and the body’s ability to neutralize them. The chemical reactions involving MGO can generate these damaging free radicals, leading to inflammation and further cellular injury.
Methylglyoxal’s Role in Disease Development
The cellular damage initiated by methylglyoxal is implicated in the development of several chronic diseases. There is a strong association between elevated MGO levels and diabetes mellitus. In individuals with diabetes, higher blood glucose levels accelerate glycolysis, which in turn increases MGO production, creating a cycle that can worsen the condition and its complications like damage to nerves, kidneys, and the retina.
Its impact extends to cardiovascular health. The accumulation of AGEs can affect the structure and function of blood vessels, contributing to arterial stiffness and endothelial dysfunction. These changes are factors in the development of atherosclerosis and other cardiovascular diseases.
Research also explores links between MGO and neurodegenerative conditions, where protein modification and oxidative stress in the brain may play a role. The steady accumulation of AGEs over a lifetime is considered a contributor to the natural aging process, as these modified proteins gradually impair the function of tissues and organs.
The Body’s Detoxification Mechanisms
The human body has an efficient system to neutralize methylglyoxal called the glyoxalase system. This enzymatic pathway converts MGO into a less reactive substance using two main enzymes, glyoxalase I (Glo1) and glyoxalase II (Glo2), which work in sequence.
The detoxification process begins with glyoxalase I, which requires a cofactor molecule called glutathione (GSH). Glutathione, an important antioxidant, first reacts with a molecule of MGO. The Glo1 enzyme then acts on this intermediate complex, converting it into a compound called S-D-lactoylglutathione.
In the second step, the glyoxalase II enzyme hydrolyzes S-D-lactoylglutathione, breaking it down to release the original glutathione molecule for reuse. The other product is D-lactate, a harmless metabolite. The efficiency of this system is dependent on a sufficient supply of glutathione within the cells.