Pyruvate decarboxylase deficiency

Gas Chromatographic and Mass Spectro-metric Studies on Urinary Organic Acids in a Patient with Congenital Lactic Acidosis Due to Pyruvate Decarboxylase Deficiency Clin. Chim. Acta 77(2) 117-124 (1977) CA 87 51177s... 

Chalmers, R.A., Lawson, A.M. and Borud, O. (1977c), Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency. Clin. Chim. Acta, 11 j 117. 

Blass, J.P., Kark, R.A.P. and Engel, W.K. (1971a), Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch. Neurol, 25,449. 

Blass, J.P., Lonsdale, D., Uhlendorf, B.W. and Horn, E. (1971b), Intermittent ataxia with pyruvate decarboxylase deficiency. Lancet, i, 1302. 

Figure 5 Model of phosphorus (P) deficiency-induced physiological changes associated with the release of P-mobilizing root exudates in cluster roots of white lupin. Solid lines indicate stimulation and dotted lines inhibition of biochemical reaction sequences or mclaholic pathways in response to P deliciency. For a detailed description see Sec. 4.1. Abbreviations SS = sucrose synthase FK = fructokinase PGM = phosphoglueomutase PEP = phosphoenol pyruvate PE PC = PEP-carboxylase MDH = malate dehydrogenase ME = malic enzyme CS = citrate synthase PDC = pyruvate decarboxylase ALDH — alcohol dehydrogenase E-4-P = erythrosc-4-phosphate DAMP = dihydraxyaceConephos-phate APase = acid phosphatase.

Both methylmalonic aciduria and propionyl-CoA decarboxylase deficiency are usually accompanied by severe ketosis, hypoglycemia, and hyperglycinemia. The cause of these conditions is not entirely clear. However, methylmalonyl-CoA, which accumulates in methylmalonic aciduria, is a known inhibitor of pyruvate carboxylase. Therefore, ketosis may develop because of impaired conversion of pyruvate to oxalo-acetate. 

Pyruvate decarboxylase Ei deficiency Pyruvate decarboxylase E3 deficiency... 

Pyruvic decarboxylase controls the entry of the end products of glycolysis into the Krebs cycle. Therefore, thiamine deficiency must have dramatic consequences if no alternative pathway is available for pyruvic acid oxidation. Understandably, in the absence of an alternative pathway, thiamine deficiency leads to a block of pyruvic decarboxylation, which is the first of the two reactions of the Krebs cycle requiring thiamine. In addition, half of the thiamine content of the brain is used in that reaction. The maintenance of the integrity of the Krebs cycle is probably more important to the cell than that of the hexose monophosphate shunt. 

The most logical explanation for the increase in blood pyruvic acid is that the increase results from the blocking of pyruvic decarboxylase. However, in experiments in which blood pyruvic acid levels in thiamine-deficient animals were correlated with the changes in the adrenals, it was concluded that the increase in blood pyruvate can be correlated more closely to adrenal hypertrophy than to thiamine deficiency. Furthermore, in thiamine-deficient adrenalec-tomized and hypophysectomized animals, pyruvemia was much less than in the controls. Finally, cortisone administration increases the level of blood pyruvate. Consequently, pyruvemia in thiamine-deficient animals may result from immediate stress caused by the deficiency and from progressive block of pyruvic decarboxylase due to the slow depletion of coenzyme. 

An explanation for the pathogenesis of the lesions observed in thiamine deficiency would seem to follow logically from these biochemical observations, for in the thiamine-deficient animal, at least two enzymes involved in the Krebs cycle are blocked. The block of pyruvic decarboxylase prevents the entry of the products of glycolysis into the Krebs cycle. The block of a-ketoglutarate decarboxylase restricts the oxidation of both carbohydrates and fatty acids. A severe metabolic distortion follows, and one of the main manifestations of the distortion is a reduction of the amount of chemical energy available in the form of ATP. Clearly, those organs that suffer the most from such alterations are those that are metabolically most active, and the heart and the peripheral nervous system surely qualify as such. 

Blass, J.P. Metabolic hypothesis for selective cerebellar damage in deficiencies of pyruvate decarboxylase. (Unpublished manuscript) (1974)... 

The 2-ketoglutarate dehydrogenase (2-KGD) complex is composed of three separate enzymes 2-ketoglutarate decarboxylase, or El lipoate succi-nyltransferase, or E2 and lipoamide dehydrogenase, or E3. The complex catalyses the oxidation of 2-ketoglutarate to yield succinyl-CoA and NADH. 2-KGD deficiency together with pyruvate dehydrogenase deficiency and branched chain ketoacid decarboxylase deficiency has been ascribed to E3 deficiency because the three enzyme complexes have the E3 component in common. E3 deficiency will not be discussed. 

Diseases and disorders resulting from a deficiency of thiamine include beriben, opisthotonos (in birds), polyneuritis, hyperesthesia, bradycardia, and edema. Rather than a specific disease, beriberi may be described as a clinical state resulting from a thiamine deficiency. In body cells, thiamine pyrophosphate is required for removing carbon dioxide from various substances, including pyruvic acid. Actually, this is accomplished by a decarboxylase of which thiamine pyrophosphate is a part. Where... 

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