Evidence that the 40,000 Mr phosphoprotein influenced by high frequency synaptic stimulation is the alpha subunit of pyruvate dehydrogenase.

We have previously shown that brief periods of high frequency synaptic stimulation of the rat hippocampus influence the endogenous phosphorylation of a 40,000 Mr brain protein (Browning et al.). The results of the present study demonstrate that this brain phosphoprotein is enriched in a purified mitochondrial fraction and co-migrates with the alpha-subunit of pyruvate dehydrogenase in sodium dodecyl sulfate polyacrylamide gels. Comparisons of total and partial proteolytic fingerprints indicate that the two proteins are essentially identical. In addition, the phosphorylation of the 40,000 Mr brain protein is sensitive to both dichloroacetate and magnesium as has been reported for pyruvate dehydrogenase. Taken together these data provide persuasive evidence that the brain protein is the alpha-subunit of pyruvate dehydrogenase and thereby raise the possibility that even very short periods of synaptic activity influence an enzyme of particular importance to mitochondrial metabolism in brain.