HAGH Human

Hydroxyacylglutathione hydrolase is classified as a thiolesterase and is responsible for the hydrolysis of S-lactoyl-glutathione to reduced glutathione and D-lactate . The enzyme’s systematic name is S-(2-hydroxyacyl)glutathione hydrolase . The reaction it catalyzes is as follows:

$$S-(2-hydroxyacyl)glutathione + H_2O \rightarrow glutathione + a 2-hydroxy carboxylate$$

This reaction is essential for maintaining cellular redox balance and protecting cells from oxidative stress .

The HAGH gene is located on chromosome 16p13.3 in humans . The gene spans approximately 21.5 kilobases and consists of multiple exons . The enzyme encoded by this gene has a molecular mass of approximately 28,861 Da and consists of 260 amino acids .

Hydroxyacylglutathione hydrolase is expressed in various tissues, with high expression levels observed in the liver, kidney, and muscle tissues . The enzyme is localized primarily in the cytoplasm and mitochondria, where it performs its detoxification function .

Human recombinant hydroxyacylglutathione hydrolase is produced using recombinant DNA technology. The gene encoding the enzyme is cloned into an expression vector, which is then introduced into a suitable host organism, such as Escherichia coli. The host cells express the enzyme, which is subsequently purified using various chromatographic techniques .

Deficiency or malfunction of hydroxyacylglutathione hydrolase can lead to the accumulation of methylglyoxal, resulting in cellular damage and contributing to various diseases, including diabetes and neurodegenerative disorders . Understanding the enzyme’s structure and function is crucial for developing therapeutic strategies to mitigate these conditions.