GGT - Gamma-Glutamyltransferase | Elisa - Clia - Antibody - Protein

Background

Gamma-Glutamyltransferase (GGT) is a membrane-bound enzyme predominantly involved in the gamma-glutamyl cycle, which plays a critical role in the metabolism of glutathione and amino acids. GGT is essential for the extracellular breakdown of glutathione, facilitating the transport of amino acids and peptides into cells and contributing to cellular antioxidant defenses. The enzyme is widely distributed in the body, with the highest concentrations found in the liver, kidney, and pancreas. Its activity is crucial for maintaining intracellular levels of glutathione, which is vital for detoxification processes and protection against oxidative stress.

GGT levels in the serum are commonly measured as a diagnostic marker for liver function. Elevated serum GGT levels can indicate liver damage, bile duct obstruction, and other hepatobiliary diseases. GGT is also an important marker in assessing alcohol consumption and liver diseases related to alcohol abuse. Moreover, GGT has been implicated in various pathological conditions, including cardiovascular diseases, diabetes, and metabolic syndrome, due to its role in oxidative stress and inflammation.

Protein Structure

GGT is a glycoprotein composed of two subunits: a heavy chain and a light chain, which result from the post-translational cleavage of a single precursor polypeptide. The heavy chain anchors the enzyme to the cellular membrane, while the light chain contains the active site. The active site includes a catalytic threonine residue that is crucial for its enzymatic activity. The enzyme's structure is highly conserved across different species, underscoring its fundamental biological importance.

Classification and Subtypes

GGT belongs to the family of gamma-glutamyltransferases (EC 2.3.2.2). It is part of a broader group of enzymes involved in amino acid and peptide metabolism. While GGT itself is a well-defined entity, its isoforms can vary slightly depending on post-translational modifications and the specific tissue in which it is expressed. The primary isoform is the membrane-bound form, but soluble forms can also be detected in serum and other bodily fluids.

Function and Biological Significance

The primary function of GGT is to catalyze the transfer of the gamma-glutamyl moiety from glutathione to an acceptor amino acid, peptide, or water. This reaction is crucial for the breakdown and resynthesis of glutathione, a major antioxidant that protects cells from oxidative damage. By facilitating the breakdown of extracellular glutathione, GGT ensures the availability of cysteine, a precursor for intracellular glutathione synthesis.

GGT's role extends beyond glutathione metabolism; it is also involved in amino acid transport across the cellular membrane. This enzyme's activity contributes to the regulation of cellular redox status and protection against oxidative stress, which is essential for maintaining cellular homeostasis and preventing damage from reactive oxygen species (ROS).

Clinical Issues

Elevated GGT levels are commonly associated with liver diseases, including hepatitis, cirrhosis, and liver cancer. It is also a marker for bile duct obstruction and alcoholic liver disease. High serum GGT levels can indicate excessive alcohol consumption and have been linked to metabolic disorders such as diabetes, obesity, and cardiovascular diseases.

Conversely, low GGT activity, although rare, can lead to impaired glutathione metabolism, resulting in increased susceptibility to oxidative stress and related disorders. Genetic polymorphisms affecting GGT expression or function can influence an individual's risk of developing certain diseases and their response to environmental toxins.

Summary

Gamma-Glutamyltransferase (GGT) is a critical enzyme in glutathione metabolism and amino acid transport. It plays a vital role in maintaining cellular antioxidant defenses and overall redox balance. Clinically, GGT serves as a significant biomarker for liver function and various metabolic disorders. Understanding GGT's structure, function, and clinical implications helps in diagnosing and managing diseases related to oxidative stress and liver dysfunction.