Pyruvate dehydrogenase phosphate deficiency

A cell is deficient in pyruvate dehydrogenase phosphate phosphatase. How would such a deficiency affect cellular metabolism ... 

Pyridoxal phosphate is a cofactor required for several reactions involving amino acid interconversion. Its requirement is increased in relation to the amount of protein in the diet. Some of the deficiency symptoms can be readily correlated with their coenzyme function. Thiamin pyrophosphate is a cofactor for pyruvate dehydrogenase, the activity of which is decreased in the brain as a result of deficiency. Pantothenic acid is required not only for... 

Fig. 27.1. Scheme of the mitochondrial energy metabolism (in muscle tissue). The described deficiencies are indicated by numbers which refer to Table 27.1. PDH(-P)y (phosphorylated) pyruvate dehydrogenase c.I, cJI, c.III, c.IVy c.Vy complexes I, II, III, IV and V, respectively, of the respiratory chain CoQ, coenzyme Q cyt c, cytochrome c Cr(P)y creatine (phosphate) /MM, inner mitochondrial membrane OMM, outer mitochondrial membrane... 

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.

Pyruvate kinase deficiency is the second most common genetic deficiency that causes a hemolytic anemia (glucose 6-phosphate dehydrogenase, G6PDH, is the most common). Characteristics include ... 

Hematological Disorders. Blood related diseases include hereditary spherocytosis, pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency, and hemoglobinopathies, such as thalassemias. 

Frequency of glutathione reductase, pyruvate kinase and glucose-6-phosphate dehydrogenase deficiency in a Spanish population. 

With such an extensive knowledge base, what is the present state of our understanding of the mechanisms of this disorder Not unexpectedly, initial studies, primarily in experimental animal models, focused on the known metabolic pathways which involve thiamine. Indeed, the classical studies of Peters in 1930 (Peters, 1969) showed lactate accumulation in the brainstem of thiamine deficient birds with normalization of this in vitro when thiamine was added to the tissue. This led to the concept of the biochemical lesion of the brain in thiamine deficiency. The enzymes which depend on thiamine are shown in Fig. 14.1. They are transketolase, pyruvate and a-ketoglutarate dehydrogenase. Transketolase is involved in the pentose phosphate pathway needed to form nucleic acids and membrane lipids, including myelin. The ketoacid dehydrogenases are key enzymes of the Krebs cycle needed for energy (ATP) synthesis and also to form acetylcholine via Acetyl CoA synthesis. Decrease in activity of this cycle would result in anaerobic metabolism and lead to lactate formation (i.e., tissue acidosis) (Fig. 14.1). 

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