Pyruvate deficiency

Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. The exercise capacity of patients with muscle phos-phofiaictokinase deficiency is low, particularly on high-carbohydrate diets. By providing an alternative lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased, work capacity is improved. 

Pyruvate kinase (PK) deficiency (MIM 255200) Presumably a variety of mutations in the gene for the R (red cell) isozyme of PK... 

Hirono A et al Pyruvate kinase deficiency and other en2y-mopathies of the erythroc T e. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

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.

J. F. Johnson, C. P. Vance, and D. L. Allan, Phosphorus deficiency in Lupinus aUms altered lateral root development and enhanced expression of phosphoenol-pyruvate carboxylase. Plant Physiol. 112 31 (1996). 

Fig. 5. Spiculed red blood cells (echinocyte) in peripheral blood smear of a splenectomized patient with pyruvate kinase deficiency.

Deficiency of pyruvate kinase (PK) is the most common and well-characterized enzymatic deficiency involving the glycolytic pathway and causing hereditary he-... 

Fig. 10. Molecular and biochemical abnormalities of homozygous pyruvate kinase deficiency discovered in our laboratory.

B3. Baronciani, L., and Beutler, E., Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. Proc. Natl. Acad. Sci. U.S.A. 90,4324-4327 (1993). 

B30. B ianchi, P Terragna, C., Zappa, M., Alfinito, F and Zanella, A., Molecular characterization of L-PK gene in pyruvate kinase (PK) deficient Italian patients. Blood 84 (Suppl. 1), 14a (1994). 

B32. Bianchi, P., Zanella, A., Zappoa, M., Vercellati, C., Terragna, C., Baronciani, L., and Sirchia, G., A new point mutation G/A 1168 (Asp390-Asn) in an Italian patient with erythrocyte pyruvate kinase deficiency. Blood 86 (Suppl. 1), 133a (1995). 

K9. Kanno, H., Wei, D. C. C., Miwa, S., Chan, L. C., and Fujii, H., Identification of a 5 -splice site mutation and a missense mutation in homozygous pyruvate kinase deficiency cases found in Hong Kong. Blood 82 (Suppl. 1), 97a (1993). 

K10. Kanno, H., Balias, S. K Miwa, S., Fujii, H and Bowman, H. S., Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. Blood 83,2311-2316 (1994). 

K11. Kanno, H Fujii, H., and Miwa, S Molecular heterogeneity of pyruvate kinase deficiency identified by single strand conformational polymorphism (SSCP) analysis. Blood 84 (Suppl. 1), 13a... 

K13. Kanno, H Morimoto, M., Fujii, H., Kasugai, T., Noguchi, T., Kitamura, Y., and Miwa, S., Pri-mary structure of murine red cell type pyruvate kinase (PK) and molecular characterization of PK deficiency identified in the CBA strain. Blood 86,3205-3210 (1995). 

L2. Lakomek, M Huppke, P Neubauer, B Pekrun, A., Winkler, H., and Schroter, W., Mutations in the R-type pyruvate kinase gene and altered enzyme kinetic properties in patients with hemolytic anemia due to pyruvate kinase deficiency. Ann. Hematol. 68,253-260 (1994). 

M27. Miwa, S Kanno, H and Fujii, H Concise review Pyruvate kinase deficiency Historical perspective and recent progress of molecular genetics. Am. J. Hematol. 42,31-35 (1993). 

N5. Neubauer, B., Lakomek, M., Winkler, H., Parke, M., Hofferbert, S., Schroter, W., Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency. Blood 77, 1871-1875 (1991). 

In the 1930s, Peters and co-workers showed that thiamine deficiency in pigeons resulted in the accumulation of lactate in the brainstem [ 15]. Furthermore, they showed that the addition of small quantities of crystalline thiamine to the isolated brainstem tissue from thiamine-deficient birds in vitro resulted in normalization of lactate levels. These findings led to the formulation of the concept of the biochemical lesion in thiamine deficiency. Subsequent studies showed that the enzyme defect responsible for the biochemical lesion was a-KGDH rather than pyruvate dehydrogenase (PHDC), as had previously been presumed. a-KGDH and PHDC are major thiamine diphosphate (TDP)-dependent enzymes involved in brain glucose oxidation (Fig. 34-4). 

Most patients with pyruvate-carboxylase deficiency present with failure to thrive, developmental delay, recurrent seizures and metabolic acidosis. Lactate, pyruvate, alanine, [3-hydroxybutyrate and acetoacetate concentrations are elevated in blood and urine. Hypoglycemia is not a consistent finding despite the fact that pyruvate carboxylase is the first rate-limiting step in gluconeogenesis. 

Defects of substrate utilization. Pyruvate dehydrogenase (PDH) deficiency can cause alterations of pyruvate metabolism, as can defects of pyruvate carboxylase, as discussed earlier. Over 200 patients have been described with a disturbance of the PDH complex (PDHC) [15,16]. The clinical picture includes several phenotypes ranging from a severe, devastating metabolic disease in the neonatal period to a benign, recurrent syndrome in older children. There is considerable overlap clinically and biochemically with other disorders (see below). 

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