Glutamic–pyruvic transaminase 2 (GPT2)

Glutamic–pyruvic transaminase 2 (GPT2), also known as alanine aminotransferase 2 (ALT2), is a mitochondrial aminotransferase enzyme encoded by the GPT2 gene. It catalyzes the reversible transamination of alanine and 2-oxoglutarate to form pyruvate and glutamate, playing a crucial role in amino acid metabolism, gluconeogenesis, and the tricarboxylic acid (TCA) cycle, especially in energy-demanding tissues including liver, muscle, and brain[1][3][5][8]. Unlike GPT1 (ALT), which is cytosolic and a routine liver disease biomarker, GPT2 is predominantly mitochondrial and is essential for neuronal development, metabolic flexibility during stress, and cancer cell metabolism[2][3][5]. Loss-of-function mutations in GPT2 cause a rare autosomal recessive disorder resulting in severe intellectual disability, reduced brain growth, and progressive neurological symptoms[5][7]. Overexpression or heightened activity of GPT2 is associated with the maintenance and growth of certain cancer types, supporting its investigation as a potential, albeit challenging, therapeutic target[3].

Other names

Alanine aminotransferase 2ALT2GPT 2MRT49glutamic pyruvate transaminase (alanine aminotransferase) 2NEDSPM

Catalytic inhibition of GPT2 impairs the transamination between alanine and 2-oxoglutarate, affecting pyruvate, glutamate, and TCA cycle intermediates[3][5]. Targeting GPT2 can decrease tumorigenesis by affecting cellular metabolism, particularly under conditions requiring metabolic flexibility (e.g., in cancers relying on glutaminolysis/anaplerosis)[3].