Phosphoglycerate Mutase 1 (PGAM1) is an enzyme found in human cells that plays a role in cellular processes. Its presence is widespread across different cell types, suggesting its general involvement in maintaining normal cellular function.
PGAM1’s Role in Cellular Energy
PGAM1 contributes to glycolysis, a fundamental metabolic pathway that breaks down glucose to generate energy in the form of adenosine triphosphate (ATP). This process begins with glucose and proceeds through a series of steps, each catalyzed by specific enzymes. PGAM1 specifically acts to convert 3-phosphoglycerate to 2-phosphoglycerate.
This conversion is a reversible reaction that maintains the balance of these molecules within the cell. The step catalyzed by PGAM1 is positioned in the middle of the glycolytic pathway, influencing the flow of metabolites towards ATP. Efficient energy production through glycolysis is a basic requirement for the survival and normal function of all cells in the body.
PGAM1’s Connection to Cancer Development
Cancer cells often exhibit altered metabolism to support their rapid growth and proliferation, a phenomenon sometimes referred to as the Warburg effect. This metabolic shift involves increased reliance on glycolysis for energy production, even in the presence of oxygen, unlike healthy cells that primarily use oxidative phosphorylation. PGAM1 is frequently overexpressed and active in many types of cancer, including breast, lung, colon, and liver cancers.
Increased PGAM1 activity in cancer cells contributes to tumor growth and survival by supporting their heightened metabolic demands. PGAM1 helps coordinate glycolysis with other metabolic pathways, such as the pentose phosphate pathway, which provides building blocks for DNA and RNA synthesis, and helps manage oxidative stress. By accelerating the conversion of 3-phosphoglycerate to 2-phosphoglycerate, PGAM1 ensures a continuous supply of precursors for macromolecule biosynthesis, which is necessary for rapidly dividing cancer cells. This enhanced metabolic activity allows cancer cells to proliferate quickly and maintain their aggressive characteristics.
Strategies for Targeting PGAM1
Given its role in supporting the altered metabolism of cancer cells, PGAM1 is a potential target for therapeutic interventions. Drugs can specifically inhibit the activity of this enzyme, thereby disrupting the metabolic pathways that cancer cells depend on for survival and growth. Researchers are actively exploring various compounds that can bind to and block PGAM1, aiming to starve cancer cells of energy and essential building blocks.
Preclinical studies show that inhibiting PGAM1 can reduce tumor growth and may make cancer cells more susceptible to existing treatments like chemotherapy and radiotherapy. The development of these therapies faces challenges, including ensuring inhibitors are highly specific to PGAM1 in cancer cells to minimize unwanted effects on healthy cells. Despite these complexities, the ongoing research into PGAM1 inhibitors represents a promising direction for developing new ways to combat cancer.