What is glucose 6-phosphate isomerase (PGI)?
PGI is an essential enzyme in the glycolitic and gluconeogenesis pathways. It converts glucose 6-phosphate to fructose 6-phosphate in glycolysis and carries out the reverse reaction in gluconeogenesis. Autocrine motility factor (AMF) and neuroleukin (NLK) are closely related isozymes sharing the characteristic residue sequence of the PGI superfamily. Both AMF and NLK proteins function as monomers while PGI protein is only functional as a dimer.
Why should you care?
Without the PGI protein in the cytoplasm within your cells, you wouldn't be able to read this right now. In fact, you wouldn't be doing anything but recycling your nutrients into the ecosphere because you would be stone cold dead. Fueling your metabolism and thus your existence is dependent upon constant production of ATP or energy. Glycolysis is the beginning pathway in both fermentation and oxidative respiration, which are the two ATP generating systems your body utilizes. PGI carries out a crucial step in glycolysis and without its function subsequent steps are not possible. In addition to this, PGI helps keep you alive during lean times. Our cells only use glucose for energy and when food isn't available to be broken down into glucose an alternative source of glucose must be provided. Gluconeogenesis to the rescue! It converts fats, proteins and other non-carbohydrate molecules into glucose, which the cells can exploit for energy. Production of glucose through gluconeogenesis is also dependent on PGI catalyzing a crucial step in the pathway.
Mycobacteria require glucose as a key building block in the production of cell walls. When glucose isn't available from the environment, these bacteria depend on gluconeogenesis. Mutations in PGI renders these bacteria glucose auxotrophs. Without glucose, PGI mutants do not proliferate since they cannot utilize other nutrients to construct viable cell walls. Developing drugs to inhibit PGI has been proposed as a possible treatment in combating mycobacterial infections.
PGI mutations in humans is an autosomal recessive disorder. The gene encoding for PGI is located on the long arm of chromosome 19. Mutations of PGI result in non-spherocytic hemolytic anemia. Although it is a rare disease, it is the third most common enzymatic defect resulting in hemolysis and 0.2% of the North American population is predicted to be heterozygous for the GPI mutant. Mutations result in enzyme instability and the defect only affects mature erythrocytes because they no longer are capable of enzyme synthesis. Symptoms of the disorder range from mild to severe. Sufferers often are jaundiced, have enlarged spleens and have varying degrees of anemia. Since glucose isn't digestible by PGI mutated RBC's, it accumulates within the cells to the point where it deforms the cell membrane disrupting the oxygen carrying function of the erythrocytes. Severe cases produce mental retardation and even death.
Elevated AMF blood levels may indicate caner. The AMF protein has been implicated in cell motility and metastasis of cancerous tissue. In addition to this, excess levels of the protein were found to induce leukemia cells to stay in the proliferation cycle. Constantly reproducing cells aren't capable of differentiating and maturating as they normally would, which furthers disease progression.
This ubiquitous protein was found to have yet another medical significance. Recent findings have put forth evidence identifying PGI as the molecule eliciting the autoimmune response in rheumatoid arthritis. Apparently, PGI could be the target antigen of T-cells and the pathogenic immunoglobulins associated with the disease.
If you don't care what PGI is or does by now, then you are hopelessly apathetic. Your very life depends upon it! Not only that, but a better understanding of its diverse biological functions could potentially save lives in the future.