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Other glycolytic enzymes refers to a collective group of protein catalysts within the glycolysis pathway that are distinct from the primary rate-limiting steps, such as hexokinase, phosphofructokinase, and pyruvate kinase. This category includes essential enzymes like glucose-6-phosphate isomerase, fructose-bisphosphate aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase, phosphoglycerate mutase, and enolase (UniProt). These enzymes facilitate the stepwise anaerobic breakdown of glucose into pyruvate, a central process for generating cellular ATP and providing carbon skeletons for the synthesis of lipids, amino acids, and nucleotides. In many pathological states, particularly cancer, these enzymes are significantly upregulated to support the Warburg effect, allowing tumor cells to maintain high metabolic flux and proliferate rapidly even under hypoxic conditions (PubMed: 21376230). While they represent promising therapeutic targets for metabolic reprogramming in oncology and certain parasitic infections, their fundamental role in the energy production of nearly all human cells—especially red blood cells and neurons—presents significant challenges for achieving a safe therapeutic index without systemic toxicity (PubMed: 28256243).
Inhibition of specific enzymatic steps within the glycolytic pathway (e.g., GAPDH, Enolase, or PGAM1) to disrupt ATP production and deplete carbon intermediates required for the biosynthesis of nucleotides and amino acids (PubMed: 28256243, PubMed: 21376230).
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