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Macro-Gamma-Glutamyltransferase (Macro-GGT)

The measurement of macro-gamma-glutamyltransferase (macro-GGT) is used to aid in the investigation of increased levels of serum gamma-glutamyltransferase, especially when the etiology of enzyme increased levels is unclear.

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Macroenzymes are high-molecular-weight complexes formed by the association of enzymes with other plasma components (immunoglobulins, lipoproteins) or through self-polymerization. They typically show an increased plasma activity due to reduced clearance of the high-molecular-weight complex. This may cause diagnostic confusion. Routine enzyme measurements cannot distinguish macroenzymes from monomeric enzymes, which delays the recognition of macroenzymes. Moreover, macroenzymes are not frequently encountered and the prevalence varies from less than 0.1% to 3.5%, complicating matters further. Amylase and creatine kinase (CK) are the most common macroenzymes reported in the literature. Other reported types of macroenzymes include alkaline phosphatase (ALP), alanine aminotransferase (SGPT/ALT), aspartate aminotransferase (SGOT/AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH) and lipase.

Nevertheless, as macroenzymes are mainly considered benign, confirming the presence of a macroenzyme is important to reduce unnecessarily repeated examinations (both non-invasive and invasive) and possible therapeutic errors.

Polyethylene glycol (PEG) precipitation is considered an easy-to-use method to detect macroenzymes based on the differential solubility of the high molecular weight complexes. Other more expensive, labor-intensive and/or time-consuming tests include electrophoresis, ultrafiltration, and gel filtration chromatography, all depending on the distinct size of macroenzymes.

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