Glycolysis: The Embden‑Meyerhof‑Parnas Pathway
Concept Name
Glycolysis
Genetic Loci
Genes for glycolytic enzymes are distributed across multiple chromosomes: HK1 (10q22), PFKL (21q22.3), PKM2 (15q22).
Intracellular Cascade
cAMP/PKA pathway indirectly stimulates glycolysis by activating PFK‑2/FBPase‑2, which produces fructose‑2,6‑bisphosphate – a potent allosteric activator of PFK‑1.
Required Cofactors
Requires Mg²⁺ (for all kinase reactions) and NAD⁺ (for GAPDH step). Thiamine (B1) as TPP is required for pyruvate dehydrogenase if pyruvate enters the TCA cycle.
Histology Stains
PAS (Periodic Acid‑Schiff) stains glycogen granules in the liver and muscle; enzyme histochemistry not routinely used for glycolytic enzymes.
EM Findings
Electron microscopy of cells with high glycolytic activity shows abundant glycogen granules and mitochondria in close proximity to the endoplasmic reticulum.
Knockout Phenotype
Knockout of hexokinase‑1 (HK1) in mice is embryonic lethal due to inability to phosphorylate glucose. Tissue‑specific knockout of PKM2 in muscle results in severe exercise intolerance.
Specific Toxins
Arsenate (AsO₄³⁻) uncouples glycolysis at the GAPDH step by forming 1‑arseno‑3‑phosphoglycerate, which hydrolyzes spontaneously, bypassing ATP production.