Hereditary triose phosphate isomerase deficiency: seven new homozygous cases

Rosa, R.J. Della; Prehu, Marie-Odette; Calvin, Marie-Claude; Badoual, J; Alix, D; Girod, R.

doi:10.1007/bf00284582

Cited by 27 publications

(16 citation statements)

References 21 publications

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“…(D) Triosephosphate isomerase deficiency. The strong increase in the concentration of dihydroxyacetone phosphate as well as the relatively unchanged ATP and 2,3-bisphosphoglycerate (2,3P,G) levels are in accordance with experimental data (Eber et al, 1991;Zanella et al, 1985;Rosa et al, 1985;Vives-Corrons et al, 1978).…”

supporting

confidence: 89%

“…Calculated range of disease Properties of deficient enzymes Number of References diseased minimum range of minimum enzyme unstable kinetic change in persons survival chronic normal activity variants change isoenzyme activity disease activity Tanaka, 1990;Valentine, 1983;Board, 1978;Rijksen, 1983;Miwa, 1985;Paglia, 1981;Necheles, 1970Tanka, 1990Paglia, 1974;Zanella, 1980;Neubauer, 1990;Arnold, 1973Tanka, 1990Vora, 1983;Valentine, 1984 ;Fogelfeld, 1990Kishi, 1987Miwa, 1981 ;Valentine, 1984Eber, 1979Valentine, 1984;Rosa, 1985 ;Zanella, 1985Waller, 1974Tanaka, 1990Maeda, 1991 ;Fujii, 1980Fujii, , 1992Valentine, 1984Schroter, 1965Rosa, 1973Rosa, , 1978Buc, 1974;Rosa, 1989;Tanaka, 1990 Syllm- Rapoport, 1965…”

Section: Enzymementioning

confidence: 99%

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Use of Mathematical Models for Predicting the Metabolic Effect of Large-Scale Enzyme Activity Alterations. Application to Enzyme Deficiencies of Red Blood Cells

Schuster

Holzhütter

1995

Eur J Biochem

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There are numerous examples showing that the metabolism of cells can be severely impaired if the activity of only one of the participating enzymes undergoes large-scale alterations, resulting, for example, from spontaneous mutations (inherited or aquired enzymopathies), the administration of toxic drugs or self-inactivation of enzymes during cell aging. However, a quantitative relationship between the degree of enzyme deficiency and the extent of metabolic dysfunction is very difficult to establish by experimental means. An alternative is to tackle this problem by mathematical modelling. Our approach is based on a comprehensive mathematical model of the energy and redox metabolism for human erythrocytes. We calculate stationary states of the cell metabolism, varying the activity of each of the participating enzymes by several orders of magnitude. The metabolic states are then evaluated in terms of a performance function which relates the metabolic variables to the overall functional fitness of the cell. The performance function for the erythrocyte takes into account the homeostasis of three essential metabolic variables : the energetic state (ATP), the reductive capacity (reduced glutathione), and the osmotic state. Based on the behaviour of the performance function at varying enzyme activities, we estimate those ranges of enzyme activities, in which the metabolic alterations should be either tolerable, associated with non-chronic or chronic diseases, or letal. For most enzymopathies, the experimental and clinical observations can be satisfactorily rationalized by the computational results. Moreover, a surprisingly high correlation is found between the range of the activity range where disease is predicted by the model and the observed number of diseased probands.Another objective of our study was to contribute to the theory of metabolic control. The well-elaborated concept of the metabolic control theory is restricted to (infinitely) small activity alterations. In order to quantify the metabolic effect of finite (large-scale) changes in the activity of an enzyme, we propose, as a control measure, the effective activity Em, defined as the relative activity of an enzyme (with respect to the activity in a reference state) required to bring about a change in the stationary value of a metabolic variable by the (finite) factor a. We demonstrate that none of the existing extrapolation methods using the conventional control coefficient is capable to provide reliable predictions of the effective activities for all enzymes of erythrocyte metabolism.

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supporting

confidence: 89%

Section: Enzymementioning

confidence: 99%

Use of Mathematical Models for Predicting the Metabolic Effect of Large-Scale Enzyme Activity Alterations. Application to Enzyme Deficiencies of Red Blood Cells

Schuster

Holzhütter

1995

Eur J Biochem

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“…In addition, patients display progressive neurologic dysfunction, 55 increased susceptibility to infection, and cardiomyopathy. 56 Patients show a 20-to 60-fold increased DHAP concentration in their erythrocytes, 57 consistent with a metabolic block at the TPI step. Most affected individuals die in childhood before the age of 6 years but there are remarkable exceptions.…”

Section: Triosephosphate Isomerasementioning

confidence: 76%

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis

Wijk

Solinge

2005

Blood

277

227

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The red blood cell depends solely on the anaerobic conversion of glucose by the Embden-Meyerhof pathway for the generation and storage of high-energy phosphates, which is necessary for the maintenance of a number of vital functions. Many red blood cell enzymopathies have been described that disturb the erythrocyte's integrity, shorten its cellular survival, and result in hemolytic anemia. By far the majority of these enzymopathies are hereditary in nature. In this review, we summarize the current knowledge regarding the genetic, biochemical, and struc- IntroductionThe moment the mature red blood cell leaves the bone marrow, it is optimally adapted to perform the binding and transport of oxygen and its delivery to all tissues. This is the most important task of the erythrocyte during its estimated 120-day journey in the bloodstream. The membrane, hemoglobin, and proteins involved in metabolic pathways of the red blood cell interact to modulate oxygen transport, protect hemoglobin from oxidant-induced damage, and maintain the osmotic environment of the cell. The biconcave shape of the red blood cell provides an optimal area for respiratory exchange. The latter requires passage through microcapillaries, which is achieved by a drastic modification of its biconcave shape, made possible only by the loss of the nucleus and cytoplasmic organelles and, consequently, the ability to synthesize proteins. 1 During their intravascular lifespan, erythrocytes require energy to maintain a number of vital cell functions. These include (1) maintenance of glycolysis; (2) maintenance of the electrolyte gradient between plasma and red cell cytoplasm through the activity of adenosine triphosphate (ATP)-driven membrane pumps; (3) synthesis of glutathione and other metabolites; (4) purine and pyrimidine metabolism; (5) maintenance of hemoglobin's iron in its functional, reduced, ferrous state; (6) protection of metabolic enzymes, hemoglobin, and membrane proteins from oxidative denaturation; and (7) preservation of membrane phospholipid asymmetry. Because of the lack of nuclei and mitochondria, mature red blood cells are incapable of generating energy via the (oxidative) Krebs cycle. Instead, erythrocytes depend on the anaerobic conversion of glucose by the Embden-Meyerhof pathway for the generation and storage of high-energy phosphates (Figure 1). Moreover, erythrocytes possess a unique glycolytic bypass for the production of 2,3-bisphosphoglycerate (2,3-DPG), the RapoportLuebering shunt. This shunt bypasses the phosphoglycerate kinase (PGK) step and accounts for the synthesis and regulation of 2,3-DPG levels that decrease hemoglobin's affinity for oxygen. 2 In addition, 2,3-DPG constitutes an energy buffer.A number of red blood cell enzymopathies have been described in the Embden-Meyerhof pathway. [3][4][5][6] The lack of characteristic changes in red blood cell morphology differentiates the glycolytic enzymopathies from erythrocyte membrane defects and most hemoglobinopathies. In general, red blood cell enzymopathies cause chronic n...

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“…The enzyme activity in erythrocytes of the allele carriers decreases and amounts to 3–10% of that in the cells of healthy donors [8, 11, 12]. They develop neurodegenerative disorders, cardiomyopathy, muscle disorders, and, less often, hemolytic anemia [11].…”

Section: Introductionmentioning

confidence: 99%

Real-Time Interaction between TVR and the TATA Box of the Human Triosephosphate Isomerase Gene Promoter in the Norm and Pathology

et al. 2014

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The TATA-binding protein (TBP) is a key part of the transcription complex of RNA polymerase II. Alone or as a part of the basal transcription factor TFIID, TBP binds the TATA box located in the core region of the TATA-containing promoters of class II genes. Previously, we studied the effects of single nucleotide polymorphisms (SNPs) on TBP/TATA-box interactions using gel retardation assay. It was demonstrated that most SNPs in the TATA boxes of some human gene promoters cause a 2- to 4-fold decrease in TBP/TATA affinity, which is associated with an increased risk of hereditary diseases, such as β thalassemias of diverse severity, hemophilia B Leyden, myocardial infarction, thrombophlebitis, lung cancer, etc. In this work, the process of TBP/TATA complex formation has been studied in real time by a stopped-flow technique using recombinant human TBP and duplexes, which were identical to the TATA box of the wild-type and a SNP-containing triosephosphate isomerase gene promoter and were fluorescently labeled by the Cy3/Cy5 FRET pair. It has been demonstrated for the first time that real-time binding of TBP to the TATA box of the TPI gene promoter is complete within 10 s and is described by a single-stage kinetic model. The complex formation of TBP with the wild-type TATA box occurs 5.5 times faster and the complex dissociation occurs 31 times slower compared with the SNPcontaining TATA box. Within the first seconds of the interaction, TBP binds to and simultaneously bends the TATA box. Importantly, the TATA box of the wild-type TPI gene promoter requires lower TBP concentrations compared to the TATA box containing the -24T → G SNP, which is associated with neurological and muscular disorders, cardiomyopathy, and other diseases.

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Hereditary triose phosphate isomerase deficiency: seven new homozygous cases

Cited by 27 publications

References 21 publications

Use of Mathematical Models for Predicting the Metabolic Effect of Large-Scale Enzyme Activity Alterations. Application to Enzyme Deficiencies of Red Blood Cells

Use of Mathematical Models for Predicting the Metabolic Effect of Large-Scale Enzyme Activity Alterations. Application to Enzyme Deficiencies of Red Blood Cells

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis

Real-Time Interaction between TVR and the TATA Box of the Human Triosephosphate Isomerase Gene Promoter in the Norm and Pathology

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