Pyruvic abnormal metabolization

Lactate, pyruvate, acetoacetate (ACAC) and 3-hydroxybutyrate ( ) are intermediary metabolites that normally occur in blood and play an essential role in energy production. Their accumulation in blood is a frequent cause of metabolic acidosis in children. The determination of these metabolites in biological fluids is useful in the early detection, diagnosis and treatment follow-up of abnormalities such as those of ... 

Early studies showed that the development of neurological abnormalities in thiamin deficiency did not follow the same time course as the impairment of pyruvate and 2-oxoglutarate dehydrogenase or transketolase activities. The brain regions in which metabolic disturbances are most marked were not those that are vulnerable to anatomical lesions. These studies suggested a function for thiamin in the nervous system other than its coenzyme role. 

An important theoretically based consideration, especially with competitive inhibitors, is that the substrates of the inhibited enzyme should not accumulate and counteract the inhibition. The biological effect of glypho-sate is aided by the multiple metabolic fates of PEP and the instability to phosphatase action of the second substrate, shikimate S-phosphate. " Similarly, pyruvate is an important constituent of the central metabolic pathways and is unlikely to reach abnormally high concentrations if ALS is inhibited. 

The clinical syndrome of beri-beri is seen sporadicedly in Nigeria, and an aetiological relationship to thiamine deficiency presumed from the therapeutic response to this vitamin. An implied relationship to the W. African ataxic neuropathy is sometimes suggested, but has been rejected because abnormalities of pyruvate metabolism are usually slight [39]. 

It is somewhat difficult to be sure of the precise diagnostic criteria included in some published reports, but since some at least of the reported conditions are genetically determined, it is reasonable to assume that they may be the clinical expression of inborn metabolic errors, as in Refsum s disease. There have been at least two reports describing abnormalities of pyruvate metabolism in Dejerine-Sottas disease [143, 144]. The latter authors concluded that at least in some of their patients abnormal pyruvate tolerance was secondary to dietary thiamine deficiency. 

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