The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Mulchand S. Patel - One of the best experts on this subject based on the ideXlab platform.
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Dysregulated Pyruvate Dehydrogenase Complex in Zucker diabetic fatty rats.
American journal of physiology. Endocrinology and metabolism, 2007Co-Authors: Christoph M. Schummer, Mulchand S. Patel, Ulrich Werner, Norbert Tennagels, Dieter Schmoll, Guido Haschke, Hans-paul Juretschke, Martin Gerl, Werner Kramer, Andreas W. HerlingAbstract:The mitochondrial Pyruvate Dehydrogenase Complex (PDC) is inactivated in many tissues during starvation and diabetes. We investigated carbohydrate oxidation (CHO) and the regulation of the PDC in l...
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regulation of the Pyruvate Dehydrogenase Complex
Biochemical Society Transactions, 2006Co-Authors: Mulchand S. Patel, Lioubov G. KorotchkinaAbstract:The PDC (Pyruvate Dehydrogenase Complex) plays a central role in the maintenance of glucose homoeostasis in mammals. The carbon flux through the PDC is meticulously controlled by elaborate mechanisms involving post-translational (short-term) phosphorylation/dephosphorylation and transcriptional (long-term) controls. The former regulatory mechanism involving multiple phosphorylation sites and tissue-specific distribution of the dedicated kinases and phosphatases is not only dependent on the interactions among the catalytic and regulatory components of the Complex but also sensitive to the intramitochondrial redox state and metabolite levels as indicators of the energy status. Furthermore, differential transcriptional controls of the regulatory components of PDC further add to the Complexity needed for long-term tuning of PDC activity for the maintenance of glucose homoeostasis during normal and disease states.
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eLS - Pyruvate Dehydrogenase Complex
Encyclopedia of Life Sciences, 2006Co-Authors: Mulchand S. Patel, Lioubov G. KorotchkinaAbstract:Pyruvate Dehydrogenase Complex (PDC) is a highly organized multienzyme Complex that plays a key role in glucose metabolism providing a direct link between glycolysis and the tricarboxylic acid cycle. PDC is tightly regulated according to changing demands in glucose consumption in different tissues and under different nutritional and pathophysiological conditions. Keywords: Pyruvate Dehydrogenase; regulation by phosphorylation/dephosphorylation; genetic defects; Pyruvate Dehydrogenase deficiency; glucose metabolism
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Human defects of the Pyruvate Dehydrogenase Complex
Alpha-Keto Acid Dehydrogenase Complexes, 1996Co-Authors: Douglas S. Kerr, Isaiah D. Wexler, Amporn Tripatara, Mulchand S. PatelAbstract:Deficiency of the Pyruvate Dehydrogenase Complex (PDC), a critical enzyme of energy metabolism, would appear incompatible with survival, particularly in the intrauterine environment where energy production depends primarily on glucose oxidation. The now well-established occurrence of these defects presents a challenge to provide physiological explanations of what factors determine survival and adaptation of affected individuals. Unfortunately, for most affected individuals, deleterious effects on the central nervous system are severe. Biochemical and genetic explanations for why this group of disorders is so heterogeneous are beginning to emerge. Several reviews concerning clinical, biochemical, and genetic features of PDC deficiency and related disorders have been published recently (Robinson, 1995; Kerr and Zinn, 1995; Dahl, 1995; Patel and Harris, 1995).
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PRETRANSLATIONAL REGULATION OF Pyruvate Dehydrogenase Complex SUBUNITS IN WHITE ADIPOSE TISSUE DURING THE SUCKLING-WEANING TRANSITION IN THE RAT
Biochemical Journal, 1995Co-Authors: J. Maury, Mulchand S. Patel, A L Kerbey, D A Priestman, Jean-philippe Girard, Pascal FerréAbstract:Total Pyruvate Dehydrogenase Complex activity is low in white adipose tissue during the suckling period and increases markedly at weaning on to a high-carbohydrate diet. This is concomitant with an increase in the E1 alpha, E1 beta and E2 subunit protein concentration and their respective mRNAs, suggesting a pretranslational control of this phenomenon. The most marked change is seen for the E1 alpha subunit (17-fold increase in protein concentration). The changes in Pyruvate Dehydrogenase Complex activity and subunit abundance induced by weaning on to a high-carbohydrate diet are precluded if the animals are weaned on to a high-fat diet, suggesting that the nutritional and/or related hormonal changes rather than a developmental stage are responsible for the observed adipose-tissue Pyruvate Dehydrogenase Complex pattern.
Niklas Darin - One of the best experts on this subject based on the ideXlab platform.
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ketogenic diet in Pyruvate Dehydrogenase Complex deficiency short and long term outcomes
Journal of Inherited Metabolic Disease, 2017Co-Authors: Kalliopi Sofou, Maria Dahlin, Tove Hallbook, Marie Lindefeldt, Gerd Viggedal, Niklas DarinAbstract:Objectives Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with Pyruvate Dehydrogenase Complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.
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Ketogenic diet in Pyruvate Dehydrogenase Complex deficiency: short‐ and long‐term outcomes
Journal of inherited metabolic disease, 2017Co-Authors: Kalliopi Sofou, Maria Dahlin, Tove Hallbook, Marie Lindefeldt, Gerd Viggedal, Niklas DarinAbstract:Objectives Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with Pyruvate Dehydrogenase Complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.
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ketogenic diet in Pyruvate Dehydrogenase Complex deficiency short and long term outcomes
Journal of Inherited Metabolic Disease, 2017Co-Authors: Kalliopi Sofou, Maria Dahlin, Tove Hallbook, Marie Lindefeldt, Gerd Viggedal, Niklas DarinAbstract:Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with Pyruvate Dehydrogenase Complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. Pediatric patients diagnosed with Pyruvate Dehydrogenase Complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed. Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe—except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients. Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.
Yoshiharu Shimomura - One of the best experts on this subject based on the ideXlab platform.
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Activities of liver Pyruvate Dehydrogenase Complex and 3-hydroxyacyl-CoA Dehydrogenase in sand rat (Psammomys obesus).
Life sciences, 1997Co-Authors: Naoya Nakai, Gregory Collier, Yuzo Sato, Yoshiharu Oshida, Noriaki Fujitsuka, Yoshiharu ShimomuraAbstract:The sand rat (Psammomys obesus) is an animal model for non-insulin dependent diabetes mellitus, which is induced by a regular chow diet. The total activity of liver Pyruvate Dehydrogenase Complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA Dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats. These metabolic conditions may be related to the predisposition of the animals towards diabetes. Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver Pyruvate Dehydrogenase Complex and in increasing the activity of liver 3-hydroxyacyl-CoA Dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.
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Effects of aging on the activities of Pyruvate Dehydrogenase Complex and its kinase in rat heart
Life sciences, 1997Co-Authors: Naoya Nakai, Yuzo Sato, Yoshiharu Oshida, Noriaki Fujitsuka, Atsushi Yoshimura, Satoru Sugiyama, Yoshiharu ShimomuraAbstract:Effects of aging on the activities of heart Pyruvate Dehydrogenase Complex and Pyruvate Dehydrogenase kinase were examined using 7, 35 and 60 wk old rats. Aging did not affect the total activity of Pyruvate Dehydrogenase Complex but decreased the activity state (percentage of active form) of the Complex in rats under the fed condition (52%, 36% and 26% for 7, 35 and 60 wk old rats, respectively). This decrease in the Complex activity with aging was suggested to be associated with an age-related decrease in the blood glucose disposal. Starvation for 24 h decreased the activity state to less than 3% in all of the age groups. The activity of Pyruvate Dehydrogenase kinase associated with the Complex was not related to the alteration in the activity state of the Complex; the kinase activity was slightly lower in 60 wk old rats than in the younger rats under the fed condition and activation of the kinase by starvation was greater in the younger rats. The mechanism for the decrease in activity of Pyruvate Dehydrogenase Complex was discussed on the basis of glucose and fatty acid utilization of heart muscle cells.
Ian R. Mackay - One of the best experts on this subject based on the ideXlab platform.
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ENZYME INHIBITORY AUTOANTIBODIES TO Pyruvate Dehydrogenase Complex IN PRIMARY BILIARY CIRRHOSIS : APPLICATIONS OF A SEMIAUTOMATED ASSAY
Hepatology, 1994Co-Authors: Khay‐lin Teoh, Merrill J. Rowley, Helen Zafirakis, E. Rolland Dickson, Russell H. Wiesner, M. Eric Gershwin, Ian R. MackayAbstract:Sera from patients with primary biliary cirrhosis inhibit the activity of the mitochondrial Pyruvate Dehydrogenase Complex. We utilized this effect to develop a simple, miniaturized, semiautomated spectrophotometric assay as a diagnostic aid. The sera studied were from 71 patients with primary biliary cirrhosis and 62 other subjects. The assays included enzyme inhibition, immunofluorescence on HEp-2 cells, enzyme-linked immunosorbent assay using recombinant Pyruvate Dehydrogenase Complex-E2 and immunoblotting on bovine heart mitochondria. With the 71 primary biliary cirrhosis sera, on which M2 antibody was detected by immunofluorescence in 64 (90%), antibodies against Pyruvate Dehydrogenase Complex were detected in 53 (83%) by means of enzyme inhibition, in 57 (89%) by means of enzyme-linked immunosorbent assay and in 60 (94%) by means of immunoblotting. Of the 64 sera positive by immunofluorescence, 60 reacted with Pyruvate Dehydrogenase Complex-E2 on immunoblotting, and the miniaturized enzyme inhibition assay was positive in 53 of these. The enzyme inhibition assay and enzyme-linked immunosorbent assay were calibrated to give a specificity of 100%. At this level, the sensitivities for detection of Pyruvate Dehydrogenase Complex antibody were 83% and 87%, respectively. We found no significant changes in levels of reactivity with the enzyme inhibition assay or enzyme-linked immunosorbent assay according to disease stage. Treatment with cyclosporine was accompanied by a significant decrease in levels of antibody to Pyruvate Dehydrogenase Complex-E2 that matched improved indexes of biochemical liver function. The semiautomated enzyme inhibition assay as described provides an additional diagnostic procedure in Pyruvate Dehydrogenase Complex; this type of assay involving specific enzyme inhibition could also be generically applied to any autoantibody antigen system. (Hepatology 1994;20:1220–1224).
Robert A. Harris - One of the best experts on this subject based on the ideXlab platform.
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Assay of the Pyruvate Dehydrogenase Complex by coupling with recombinant chicken liver arylamine N-acetyltransferase
Analytical biochemistry, 2006Co-Authors: Nam Ho Jeoung, Paresh C. Sanghani, Lanmin Zhai, Robert A. HarrisAbstract:The activity of the Pyruvate Dehydrogenase Complex has long been determined in some laboratories by coupling the production of acetyl-coenzyme A (acetyl-CoA) to the acetylation of 4-aminoazobenzene-4'-sulfonic acid by arylamine N-acetyltransferase. The assay has some advantages, but its use has been limited by the need for large amounts of arylamine N-acetyltransferase. Here we report production of recombinant chicken liver arylamine N-acetyltransferase and optimization of its use in miniaturized assays for the Pyruvate Dehydrogenase Complex and its kinase.
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Dihydrolipoamide Dehydrogenase-binding protein of the human Pyruvate Dehydrogenase Complex. DNA-derived amino acid sequence, expression, and reconstitution of the Pyruvate Dehydrogenase Complex
Journal of Biological Chemistry, 1997Co-Authors: Robert A. Harris, Melissa M. Bowker-kinley, Jingjau Jeng, Kirill M. PopovAbstract:Next Section Abstract Protein X, recently renamed dihydrolipoamide Dehydrogenase-binding protein (E3BP), is required for anchoring dihydrolipoamide Dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the Pyruvate Dehydrogenase Complexes of eukaryotes. DNA and deduced protein sequences for E3BP of the human Pyruvate Dehydrogenase Complex are reported here. With the exception of only a single lipoyl domain, the protein has a segmented multi-domain structure analogous to that of the E2 component of the Complex. The protein has 46% amino acid sequence identity in its amino-terminal region with the second lipoyl domain of E2, 38% identity in its central region with the putative peripheral subunit-binding domain of E2, and 50% identity in its carboxyl-terminal region with the catalytic inner core domain of E2. The similarity in the latter domain stands in contrast to E3BP ofSaccharomyces cerevisiae, which is quite different from its homologous transacetylase in this region. The putative catalytic site histidine residue present in the inner core domains of all dihydrolipoamide acyltransferases is replaced by a serine residue in human E3BP; thus, catalysis of coenzyme A acetylation by this protein is unlikely. Coexpression of cDNAs for E3BP and E2 resulted in the formation of an E2·E3BP subComplex that spontaneously reconstituted the Pyruvate Dehydrogenase Complex in the presence of native E3 and recombinant Pyruvate decarboxylase (E1).
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Dihydrolipoamide Dehydrogenase-binding protein of the human Pyruvate Dehydrogenase Complex. DNA-derived amino acid sequence, expression, and reconstitution of the Pyruvate Dehydrogenase Complex
The Journal of biological chemistry, 1997Co-Authors: Robert A. Harris, Melissa M. Bowker-kinley, Jingjau Jeng, Kirill M. PopovAbstract:Protein X, recently renamed dihydrolipoamide Dehydrogenase-binding protein (E3BP), is required for anchoring dihydrolipoamide Dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the Pyruvate Dehydrogenase Complexes of eukaryotes. DNA and deduced protein sequences for E3BP of the human Pyruvate Dehydrogenase Complex are reported here. With the exception of only a single lipoyl domain, the protein has a segmented multi-domain structure analogous to that of the E2 component of the Complex. The protein has 46% amino acid sequence identity in its amino-terminal region with the second lipoyl domain of E2, 38% identity in its central region with the putative peripheral subunit-binding domain of E2, and 50% identity in its carboxyl-terminal region with the catalytic inner core domain of E2. The similarity in the latter domain stands in contrast to E3BP ofSaccharomyces cerevisiae, which is quite different from its homologous transacetylase in this region. The putative catalytic site histidine residue present in the inner core domains of all dihydrolipoamide acyltransferases is replaced by a serine residue in human E3BP; thus, catalysis of coenzyme A acetylation by this protein is unlikely. Coexpression of cDNAs for E3BP and E2 resulted in the formation of an E2·E3BP subComplex that spontaneously reconstituted the Pyruvate Dehydrogenase Complex in the presence of native E3 and recombinant Pyruvate decarboxylase (E1).
