The mechanism of chondrocyte hydrogen peroxide damage. Depletion of intracellular ATP due to suppression of glycolysis caused by oxidation of glyceraldehyde-3-phosphate dehydrogenase

Exposure of articular cartilage to H₂O₂ in vitro inhibits proteoglycan synthesis in a fashion which parallels the inhibition which occurs in cartilage in animal models of acute inflammation. Our study shows that exposure to H₂O₂ also inhibits other chondrocyte functions, including total protein and DNA synthesis. Since these intracellular biosynthetic processes require adenosine triphosphate (ATP), the effect of exposure of H₂O₂ on chondrocyte ATP was measured. Exposure to H₂O₂ caused an immediate (< 2 min) dose dependent decrease in cartilage ATP levels - found to be due to the oxidative inactivation of glyceraldehyde-3-phosphate dehydrogenase (G-3-PDH). We suggest that intrachondrocyte oxidant damage occurs through oxidation of the sensitive thiol (-SH) residue at the active center of G-3-PDH, with subsequent reduction in the rate of glycolytic ATP synthesis and the intracellular concentration of ATP which is required for DNA, protein, proteoglycan and hyaluronic acid synthesis.