Differential Decrease of “Shuttle” Enzymes of Extramitochondrial NADH 2 Oxidation of Heart Muscle during Progressive Thiamine Deficiency 1,2

Summary

In spite of the apparent functioning of the a-glycerophosphate “shuttle” in heart muscle, progressive thiamine deficiency does not bring about an expected compensatory increase in the soluble cytoplasmic and the mitochondrial particle-bound a-glycerophosphate dehydrogenases. This was suggested by the previous finding that a-glycerophosphate (and also β-hydroxybutyrate) strongly stimulate mitochondrial NADH₂-cytochrome c reductase between 2 and 6 weeks of thiamine deficiency. Although the soluble cytoplasmic a-glycerophosphate dehydrogenase shows a temporary increase at the beginning of thiamine deficiency, it returns immediately to and then remains at the control level up to death. On the other hand, the level of the particle-bound enzyme gradually decreases, the onset of decrease depending on the severity of thiamine deficiency. Except for a small increase at the terminal stage of severe thiamine deficiency, mitochondrial β-hydroxybutyrate dehydrogenase level remains constant throughout the feeding of thiamine-deficient diets.