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Kirill M. Popov - One of the best experts on this subject based on the ideXlab platform.
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tissue specific kinase expression and activity regulate flux through the Pyruvate Dehydrogenase complex
Journal of Biological Chemistry, 2019Co-Authors: Alla Klyuyeva, Natalia Y Kedishvili, Alina Tuganova, Kirill M. PopovAbstract:: The Pyruvate Dehydrogenase complex (PDC) is a multienzyme assembly that converts Pyruvate to acetyl-CoA. As Pyruvate and acetyl-CoA play central roles in cellular metabolism, understanding PDC regulation is pivotal to understanding the larger metabolic network. The activity of mammalian PDC is regulated through reversible phosphorylation governed by at least four isozymes of Pyruvate Dehydrogenase kinase (PDK). Deciphering which kinase regulates PDC in organisms at specific times or places has been challenging. In this study, we analyzed mouse strains carrying targeted mutations of individual isozymes to explore their role in regulating PDC activity. Analysis of protein content of PDK isozymes in major metabolic tissues revealed that PDK1 and PDK2 were ubiquitously expressed, whereas PDK3 and PDK4 displayed a rather limited tissue distribution. Measurement of kinase activity showed that PDK1 is the principal isozyme regulating hepatic PDC. PDK2 was largely responsible for inactivation of PDC in tissues of muscle origin and brown adipose tissue (BAT). PDK3 was the principal kinase regulating Pyruvate Dehydrogenase activity in kidney and brain. In a well-fed state, the tissue levels of PDK4 protein were fairly low. In most tissues tested, PDK4 ablation had little effect on the overall rates of inactivation of PDC in kinase reaction. Taken together, these data strongly suggest that the activity of PDC is regulated by different isozymes in different tissues. Furthermore, it appears that the overall flux through PDC in a given tissue largely reflects the properties of the PDK isozyme that is principally responsible for the regulation of PDC activity in that tissue.
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structure of Pyruvate Dehydrogenase kinase novel folding pattern for a serine protein kinase
Journal of Biological Chemistry, 2001Co-Authors: Nicklaus C Steussy, Kirill M. Popov, Melissa M Bowkerkinley, Robert B Sloan, Robert A Harris, Jean A HamiltonAbstract:Abstract The structure of mitochondrial Pyruvate Dehydrogenase kinase isozyme 2 is of interest because it represents a family of serine-specific protein kinases that lack sequence similarity with all other eukaryotic protein kinases. Similarity exists instead with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases. The 2.5-A crystal structure reported here reveals that Pyruvate Dehydrogenase kinase isozyme 2 has two domains of about the same size. The N-terminal half is dominated by a bundle of four amphipathic α-helices, whereas the C-terminal half is folded into an α/β sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very similar to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinases and ATPases.
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starvation increases the amount of Pyruvate Dehydrogenase kinase in several mammalian tissues
Archives of Biochemistry and Biophysics, 2000Co-Authors: Pengfei Wu, Kirill M. Popov, Paul V. Blair, Juichi Sato, Jerzy Jaskiewicz, Robert A HarrisAbstract:Abstract Covalent modification of the Pyruvate Dehydrogenase complex provides an important regulatory mechanism for controlling the disposal of glucose and other compounds metabolized to Pyruvate. Regulation of the complex by this mechanism is achieved in part by tissue-specific expression of the genes encoding isoenzymes of Pyruvate Dehydrogenase kinase (PDK). Starvation is known from our previous work to increase PDK activity of heart and skeletal muscle by increasing the amount of PDK isoenzyme 4 (PDK4) present in these tissues. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to starvation. PDK4 and PDK2 message levels were also increased by starvation in the two tissues examined (liver and kidney), suggesting enhancement of gene transcription. Changes in PDK2 message and protein were of similar magnitude, but changes in PDK4 message were greater than those in PDK4 protein, suggesting regulation at the level of translation. In contrast to these tissues, starvation had little or no effect on PDK2 and PDK4 protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by starvation. The findings of this study indicate that increased expression of PDK isoenzymes is an important mechanism for bringing about inactivation of the Pyruvate Dehydrogenase complex during starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity of neuronal tissue to utilize glucose for energy during starvation.
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mechanism responsible for inactivation of skeletal muscle Pyruvate Dehydrogenase complex in starvation and diabetes
Diabetes, 1999Co-Authors: K Inskeep, Kirill M. Popov, Melissa M Bowkerkinley, Robert A HarrisAbstract:Regulation of the activity of the Pyruvate Dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis. Activation of the complex promotes disposal of glucose, whereas inactivation conserves substrates for hepatic glucose production. Starvation and diabetes induce a stable increase in Pyruvate Dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex. The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four Pyruvate Dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle. Refeeding starved rats and insulin treatment of diabetic rats decreased Pyruvate Dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria. Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes. These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the Pyruvate Dehydrogenase complex in these metabolic conditions. It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in Pyruvate Dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle. Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
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starvation and diabetes increase the amount of Pyruvate Dehydrogenase kinase isoenzyme 4 in rat heart
Biochemical Journal, 1998Co-Authors: Pengfei Wu, Kirill M. Popov, Juichi Sato, Jerzy Jaskiewicz, Yu Zhao, Robert A HarrisAbstract:This study investigated whether conditions known to alter the activity and phosphorylation state of the Pyruvate Dehydrogenase complex have specific effects on the levels of isoenzymes of Pyruvate Dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the Pyruvate Dehydrogenase complex in rat heart.
Robert A Harris - One of the best experts on this subject based on the ideXlab platform.
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Metabolic Connection of Inflammatory Pain: Pivotal Role of a Pyruvate Dehydrogenase Kinase-Pyruvate Dehydrogenase-Lactic Acid Axis.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015Co-Authors: Mithilesh Kumar Jha, Nam Ho Jeoung, Robert A Harris, Dong Ho Park, Hyun Kook, In-kyu Lee, Gyun Jee Song, Maan-gee Lee, Kyoungho SukAbstract:Pyruvate Dehydrogenase kinases (PDK1–4) are mitochondrial metabolic regulators that serve as decision makers via modulation of Pyruvate Dehydrogenase (PDH) activity to convert Pyruvate either aerobically to acetyl-CoA or anaerobically to lactate. Metabolic dysregulation and inflammatory processes are two sides of the same coin in several pathophysiological conditions. The lactic acid surge associated with the metabolic shift has been implicated in diverse painful states. In this study, we investigated the role of PDK-PDH-lactic acid axis in the pathogenesis of chronic inflammatory pain. Deficiency of Pdk2 and/or Pdk4 in mice attenuated complete Freund9s adjuvant (CFA)-induced pain hypersensitivities. Likewise, Pdk2/4 deficiency attenuated the localized lactic acid surge along with hallmarks of peripheral and central inflammation following intraplantar administration of CFA. In vitro studies supported the role of PDK2/4 as promoters of classical proinflammatory activation of macrophages. Moreover, the pharmacological inhibition of PDKs or lactic acid production diminished CFA-induced inflammation and pain hypersensitivities. Thus, a PDK-PDH-lactic acid axis seems to mediate inflammation-driven chronic pain, establishing a connection between metabolism and inflammatory pain. SIGNIFICANCE STATEMENT The mitochondrial Pyruvate Dehydrogenase (PDH) kinases (PDKs) and their substrate PDH orchestrate the conversion of Pyruvate either aerobically to acetyl-CoA or anaerobically to lactate. Lactate, the predominant end product of glycolysis, has recently been identified as a signaling molecule for neuron-glia interactions and neuronal plasticity. Pathological metabolic shift and subsequent lactic acid production are thought to play an important role in diverse painful states; however, their contribution to inflammation-driven pain is still to be comprehended. Here, we report that the PDK-PDH-lactic acid axis constitutes a key component of inflammatory pain pathogenesis. Our findings establish an unanticipated link between metabolism and inflammatory pain. This study unlocks a previously ill-explored research avenue for the metabolic control of inflammatory pain pathogenesis.
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role of Pyruvate Dehydrogenase kinase 4 in regulation of blood glucose levels
Korean Diabetes Journal, 2010Co-Authors: Nam Ho Jeoung, Robert A HarrisAbstract:In the well-fed state a relatively high activity of the Pyruvate Dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of Pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving Pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the Pyruvate Dehydrogenase kinases (PDKs) and the opposing Pyruvate Dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.
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structure of Pyruvate Dehydrogenase kinase novel folding pattern for a serine protein kinase
Journal of Biological Chemistry, 2001Co-Authors: Nicklaus C Steussy, Kirill M. Popov, Melissa M Bowkerkinley, Robert B Sloan, Robert A Harris, Jean A HamiltonAbstract:Abstract The structure of mitochondrial Pyruvate Dehydrogenase kinase isozyme 2 is of interest because it represents a family of serine-specific protein kinases that lack sequence similarity with all other eukaryotic protein kinases. Similarity exists instead with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases. The 2.5-A crystal structure reported here reveals that Pyruvate Dehydrogenase kinase isozyme 2 has two domains of about the same size. The N-terminal half is dominated by a bundle of four amphipathic α-helices, whereas the C-terminal half is folded into an α/β sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very similar to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinases and ATPases.
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starvation increases the amount of Pyruvate Dehydrogenase kinase in several mammalian tissues
Archives of Biochemistry and Biophysics, 2000Co-Authors: Pengfei Wu, Kirill M. Popov, Paul V. Blair, Juichi Sato, Jerzy Jaskiewicz, Robert A HarrisAbstract:Abstract Covalent modification of the Pyruvate Dehydrogenase complex provides an important regulatory mechanism for controlling the disposal of glucose and other compounds metabolized to Pyruvate. Regulation of the complex by this mechanism is achieved in part by tissue-specific expression of the genes encoding isoenzymes of Pyruvate Dehydrogenase kinase (PDK). Starvation is known from our previous work to increase PDK activity of heart and skeletal muscle by increasing the amount of PDK isoenzyme 4 (PDK4) present in these tissues. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to starvation. PDK4 and PDK2 message levels were also increased by starvation in the two tissues examined (liver and kidney), suggesting enhancement of gene transcription. Changes in PDK2 message and protein were of similar magnitude, but changes in PDK4 message were greater than those in PDK4 protein, suggesting regulation at the level of translation. In contrast to these tissues, starvation had little or no effect on PDK2 and PDK4 protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by starvation. The findings of this study indicate that increased expression of PDK isoenzymes is an important mechanism for bringing about inactivation of the Pyruvate Dehydrogenase complex during starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity of neuronal tissue to utilize glucose for energy during starvation.
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mechanism responsible for inactivation of skeletal muscle Pyruvate Dehydrogenase complex in starvation and diabetes
Diabetes, 1999Co-Authors: K Inskeep, Kirill M. Popov, Melissa M Bowkerkinley, Robert A HarrisAbstract:Regulation of the activity of the Pyruvate Dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis. Activation of the complex promotes disposal of glucose, whereas inactivation conserves substrates for hepatic glucose production. Starvation and diabetes induce a stable increase in Pyruvate Dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex. The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four Pyruvate Dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle. Refeeding starved rats and insulin treatment of diabetic rats decreased Pyruvate Dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria. Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes. These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the Pyruvate Dehydrogenase complex in these metabolic conditions. It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in Pyruvate Dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle. Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
Yasuhiro Kuroda - One of the best experts on this subject based on the ideXlab platform.
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molecular analysis of abnormal Pyruvate Dehydrogenase in a patient with thiamine responsive congenital lactic acidemia
Pediatric Research, 1994Co-Authors: Etsuo Naito, Satoshi Yoshijima, Ichiro Yokota, Eiji Takeda, Yasuhiro KurodaAbstract:Molecular Analysis of Abnormal Pyruvate Dehydrogenase in a Patient with Thiamine-Responsive Congenital Lactic Acidemia
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decrease of Pyruvate Dehydrogenase phosphatase activity in patients with congenital lactic acidemia
Clinica Chimica Acta, 1992Co-Authors: Hideaki Kobashi, Takahiko Saijo, Eiji Takeda, Etsuo Naito, Yasuhiro KurodaAbstract:Abstract We developed an assay method for Pyruvate Dehydrogenase phosphatase activity using [1- 14 C]Pyruvate and measured Pyruvate Dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the Pyruvate Dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the Pyruvate Dehydrogenase complex in these patients might be due to a reduction in Pyruvate Dehydrogenase phosphatase activity.
Lioubov G Korotchkina - One of the best experts on this subject based on the ideXlab platform.
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Pyruvate Dehydrogenase complex deficiency is linked to regulatory loop disorder in the αv138m variant of human Pyruvate Dehydrogenase
Journal of Biological Chemistry, 2018Co-Authors: Matthew J Whitley, Lioubov G Korotchkina, Mulchand S. Patel, Palaniappa Arjunan, Natalia S Nemeria, Yunhee Park, Frank Jordan, William FureyAbstract:The Pyruvate Dehydrogenase multienzyme complex (PDHc) connects glycolysis to the tricarboxylic acid cycle by producing acetyl-CoA via the decarboxylation of Pyruvate. Because of its pivotal role in glucose metabolism, this complex is closely regulated in mammals by reversible phosphorylation, the modulation of which is of interest in treating cancer, diabetes, and obesity. Mutations such as that leading to the αV138M variant in Pyruvate Dehydrogenase, the Pyruvate-decarboxylating PDHc E1 component, can result in PDHc deficiency, an inborn error of metabolism that results in an array of symptoms such as lactic acidosis, progressive cognitive and neuromuscular deficits, and even death in infancy or childhood. Here we present an analysis of two X-ray crystal structures at 2.7-A resolution, the first of the disease-associated human αV138M E1 variant and the second of human wildtype (WT) E1 with a bound adduct of its coenzyme thiamin diphosphate and the substrate analogue acetylphosphinate. The structures provide support for the role of regulatory loop disorder in E1 inactivation, and the αV138M variant structure also reveals that altered coenzyme binding can result in such disorder even in the absence of phosphorylation. Specifically, both E1 phosphorylation at αSer-264 and the αV138M substitution result in disordered loops that are not optimally oriented or available to efficiently bind the lipoyl domain of PDHc E2. Combined with an analysis of αV138M activity, these results underscore the general connection between regulatory loop disorder and loss of E1 catalytic efficiency.
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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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How dihydrolipoamide Dehydrogenase-binding protein binds dihydrolipoamide Dehydrogenase in the human Pyruvate Dehydrogenase complex.
Journal of Biological Chemistry, 2005Co-Authors: Ewa Ciszak, Anna Makal, Young Soo Hong, Ananthalakshmy K. Vettaikkorumakankauv, Lioubov G KorotchkinaAbstract:Abstract The dihydrolipoamide Dehydrogenase-binding protein (E3BP) and the dihydrolipoamide acetyltransferase (E2) component enzyme form the structural core of the human Pyruvate Dehydrogenase complex by providing the binding sites for two other component proteins, dihydrolipoamide Dehydrogenase (E3) and Pyruvate Dehydrogenase (E1), as well as Pyruvate Dehydrogenase kinases and phosphatases. Despite a high similarity between the primary structures of E3BP and E2, the E3-binding domain of human E3BP is highly specific to human E3, whereas the E1-binding domain of human E2 is highly specific to human E1. In this study, we characterized binding of human E3 to the E3-binding domain of E3BP by x-ray crystallography at 2.6-A resolution, and we used this structural information to interpret the specificity for selective binding. Two subunits of E3 form a single recognition site for the E3-binding domain of E3BP through their hydrophobic interface. The hydrophobic residues Pro133, Pro154, and Ile157 in the E3-binding domain of E3BP insert themselves into the surface of both E3 polypeptide chains. Numerous ionic and hydrogen bonds between the residues of three interacting polypeptide chains adjacent to the central hydrophobic patch add to the stability of the subcomplex. The specificity of pairing for human E3BP with E3 is interpreted from its subcomplex structure to be most likely due to conformational rigidity of the binding fragment of the E3-binding domain of E3BP and its exquisite amino acid match with the E3 target interface.
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r lipoic acid inhibits mammalian Pyruvate Dehydrogenase kinase
Free Radical Research, 2004Co-Authors: Lioubov G Korotchkina, Sukhdeep SidhuAbstract:The four Pyruvate Dehydrogenase kinase (PDK) and two Pyruvate Dehydrogenase phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate activity of the Pyruvate Dehydrogenase complex (PDC) by phosphorylation/dephosphorylation of its Pyruvate Dehydrogenase (E1) component. The effect of lipoic acids on the activity of PDKs and PDPs was investigated in purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid did not significantly affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1 > PDK4 ∼ PDK2 > PDK3 for R-LA). Since lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the presence of E1 alone, dissociation of PDK from the lipoyl domains of dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a likely explanation for inhibition. The activity of PDK1 towards phosphorylation sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R-lipoic acid, thus excluding protection of ...
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Regulation of mammalian Pyruvate Dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases
Experimental & Molecular Medicine, 2001Co-Authors: Lioubov G KorotchkinaAbstract:This review summarizes the recent developments on the regulation of human Pyruvate Dehydrogenase complex (PDC) by site-specific phosphorylation by four kinases. Mutagenic analysis of the three phosphorylation sites of human Pyruvate Dehydrogenase (E1) showed the site-independent mechanism of phosphorylation as well as site-independent dephosphorylation of the three phosphorylation sites and the importance of each phosphorylation site for the inactivation of E1. Both the negative charge and size of the group introduced at site 1 were involved in human E1 inactivation. Mechanism of inactivation of E1 was suggested to be site-specific. Phosphorylation of site 1 affected E1 interaction with the lipoyl domain of dihydrolipoamide acetyltransferase, whereas phosphorylation site 3 appeared to be closer to the thiamine pyrophosphate (TPP)-binding region affecting coenzyme interaction with human E1. Four isoenzymes of Pyruvate Dehydrogenase kinase (PDK) showed different specificity for the three phosphorylation sites of E1. All four PDKs phosphorylated sites 1 and 2 in PDC with different rates, and only PDK1 phosphorylated site 3. PDK2 was maximally stimulated by the reduction/acetylation of the lipoyl groups of E2. Presence of the multiple phosphorylation sites and isoenzymes of PDK is important for the tissue-specific regulation of PDC under different physiological conditions.
Etsuo Naito - One of the best experts on this subject based on the ideXlab platform.
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molecular analysis of abnormal Pyruvate Dehydrogenase in a patient with thiamine responsive congenital lactic acidemia
Pediatric Research, 1994Co-Authors: Etsuo Naito, Satoshi Yoshijima, Ichiro Yokota, Eiji Takeda, Yasuhiro KurodaAbstract:Molecular Analysis of Abnormal Pyruvate Dehydrogenase in a Patient with Thiamine-Responsive Congenital Lactic Acidemia
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decrease of Pyruvate Dehydrogenase phosphatase activity in patients with congenital lactic acidemia
Clinica Chimica Acta, 1992Co-Authors: Hideaki Kobashi, Takahiko Saijo, Eiji Takeda, Etsuo Naito, Yasuhiro KurodaAbstract:Abstract We developed an assay method for Pyruvate Dehydrogenase phosphatase activity using [1- 14 C]Pyruvate and measured Pyruvate Dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the Pyruvate Dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the Pyruvate Dehydrogenase complex in these patients might be due to a reduction in Pyruvate Dehydrogenase phosphatase activity.
