Moniliformin

Moniliformin reversibly inhibits the enzymes pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase by competing for the binding site of pyruvate. This interferes with the tricarboxylic acid cycle by preventing the necessary incorporation of pyruvate and oxidation of the alpha-ketoglutarate intermediate. Moniliformin has also been shown to interfere with carbohydrate metabolism by inhibiting transketolase and aldose reductase. Moniliformin causes the necrosis of human chondrocytes in cartilage. It does so by increasing the expression of matrix catabolic enzymes, such as MMP-1 and MMP-13, and decreasing the syntheses of extracellular matrix components such as aggrecan and type II collage. This accelerates the catabolism of the extracellular matrix in articular cartilages, inducing a loss of cartilage function and eventually leading to cartilage degradation. Moniliformin is also known to cause DNA damage, inducing chromatid breaks, chromosome breaks, and chromatid exchanges. (A3075, A3076, A3077)

The main symptoms of acute moniliformin toxication in animals are muscular weakness, respiratory stress, myocardial degeneration, as well as some histopathological changes in organs such as the kidneys, the lungs and the pancreas, followed by coma and death. Kashin-Beck disease is characterized by joint pain, with restriction of movement and joint enlargement. (A3077)