PGAM1 is a dimeric enzyme that exists in isoforms (e.g., brain (BB), muscle (MM), and hybrid (MB) forms) and is essential for glycolysis. Key biochemical features include:
Recombinant PGAM1 proteins (e.g., His-tagged versions expressed in E. coli) are widely used in biochemical assays to study glycolytic flux and metabolic reprogramming .
Genetic knockout (KO) and heterozygous (Pgam1+/−) models have revealed PGAM1’s essential role in development and metabolism.
PGAM1 is critical for T cell activation. Pgam1 deletion in T cells leads to:
Reduced glycolysis: Impaired conversion of 3-PG to 2-PG, limiting energy production during activation .
Impaired differentiation: Defective Th1/Th17 responses, as seen in experimental autoimmune encephalomyelitis (EAE) models .
Diminished inflammation: Reduced eosinophil/neutrophil infiltration in allergic airway inflammation models .
In Sertoli cells (SCs), PGAM1 regulates spermatogonial stem cell (SSC) fate:
PGAM1 overexpression: Upregulates genes promoting SSC proliferation.
PGAM1 knockdown: Downregulates proliferation genes, favoring differentiation .
PGAM1 protects against ischemic injury:
Tat-PGAM1 treatment: Reduces neuronal death, oxidative stress, and microglial activation in spinal cord ischemia models .
PGAM1 overexpression correlates with aggressive tumors (e.g., uveal melanoma):
Heterozygous Pgam1+/− mice exhibit:
Normal glucose tolerance: Despite 50% reduced PGAM1 activity .
No significant lipid or protein abnormalities: Suggesting compensatory metabolic pathways .
PGAM1 belongs to the phosphoglycerate mutase family and is a dimeric enzyme. It exists in different isoforms, including a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB) found in various tissues . The enzyme is essential for efficient energy production and is involved in the metabolism of glucose and 2,3-bisphosphoglycerate (2,3-BPGA) .
Recombinant mouse PGAM1 is a bioactive protein that has been engineered for research purposes. It is typically expressed in E. coli and purified using conventional chromatography techniques . The recombinant version often includes a His-tag at the N-terminus to facilitate purification and detection .
Recombinant PGAM1 is used in various biochemical and physiological studies to understand its role in metabolism and disease. For instance, it has been studied in the context of cancer metabolism, where it is known to promote tumor progression by inducing immunosuppressive M2 macrophages . This makes PGAM1 a potential target for cancer therapy, particularly in breast cancer .