PGAM4 Inhibitors

Chemicals classified as PGAM4 inhibitors encompass a diverse array of compounds that can indirectly influence the activity of this enzyme by modulating various metabolic pathways, particularly those involved in glycolysis and gluconeogenesis. Compounds such as 2,3-bisphosphoglycerate and fluoride ions can modify the enzyme's conformation or the stability of its substrate complexes, thus altering its function. Others like alpha-ketoglutarate and oxaloacetate participate in the Krebs cycle and can affect the redox state of cells, which indirectly impacts enzymes like PGAM4 by changing the availability of cofactors such as NADH.

The second class of these inhibitors includes small molecules like iodoacetate and N-ethylmaleimide, which can chemically modify amino acid residues within the enzyme, potentially affecting its activity. Additionally, metabolic intermediates such as citrate and arsenate can disrupt normal substrate handling by PGAM4 or its related enzymatic pathways. Citrate serves as an allosteric inhibitor in glycolysis, potentially increasing substrate availability for PGAM4, while arsenate directly competes with phosphate, leading to the formation of unstable intermediates that can impair the enzyme's function. Substances like berberine and 3-bromopyruvate impact the enzyme indirectly by altering the overall flux through glycolysis, thereby affecting the concentration of substrates and products that could be critical for PGAM4's activity. These compounds demonstrate the interconnected nature of metabolic enzyme regulation and how altering one component of a pathway can have cascading effects on other enzymes, including PGAM4.