Lactoylglutathione lyase

Lactoylglutathione lyase

Structure of pyruvaldehyde, a substrate for lactoylglutathione lyase.

Lactoylglutathione lyase, also known as glyoxalase I, is an enzyme that plays a crucial role in the glyoxalase system, which is involved in the detoxification of methylglyoxal, a cytotoxic byproduct of metabolism. This enzyme catalyzes the conversion of hemithioacetal, formed from methylglyoxal and glutathione, into S-lactoylglutathione.

Function

Lactoylglutathione lyase is responsible for the first step in the glyoxalase pathway. It facilitates the isomerization of the hemithioacetal adduct of methylglyoxal and glutathione into S-lactoylglutathione. This reaction is essential for cellular detoxification processes, as methylglyoxal is a reactive aldehyde that can modify proteins and nucleic acids, leading to cellular damage.

Mechanism

The enzyme operates by binding to the hemithioacetal substrate and catalyzing its conversion through a series of proton transfers and rearrangements. The active site of lactoylglutathione lyase contains metal ions, such as zinc or magnesium, which are critical for its catalytic activity. These metal ions stabilize the transition state and facilitate the isomerization process.

Biological significance

Lactoylglutathione lyase is found in a wide range of organisms, including bacteria, plants, and animals. Its activity is crucial for maintaining cellular homeostasis and protecting cells from oxidative stress. In humans, the enzyme is expressed in various tissues and is particularly important in the liver and kidneys, where detoxification processes are prominent.

Clinical relevance

Alterations in the activity of lactoylglutathione lyase have been associated with several pathological conditions. For instance, reduced activity of this enzyme can lead to the accumulation of methylglyoxal, contributing to the development of diabetes-related complications, such as neuropathy and nephropathy. Conversely, overexpression of glyoxalase I has been observed in certain cancers, where it may contribute to the survival and proliferation of cancer cells by mitigating oxidative stress.

Related pages

• Glyoxalase system
• Methylglyoxal
• Glutathione
• Detoxification