ピルビン酸キナーゼ。ホスホエノールトランスホスホリラーゼ
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English Journal
- Resveratrol restores sirtuin 1 (SIRT1) activity and pyruvate dehydrogenase kinase 1 (PDK1) expression after hemorrhagic injury in a rat model.
- Jian B, Yang S, Chaudry IH, Raju R.Author information Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.AbstractSevere hemorrhage leads to decreased blood flow to tissues resulting in decreased oxygen and nutrient availability affecting mitochondrial function. A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline observed after trauma hemorrhage (T-H). Our experiments led to the identification of sirtuin 1 (SIRT1) as a potential target in T-H. Administration of resveratrol (a naturally occurring polyphenol and activator of SIRT1) after T-H improved left ventricular function and tissue ATP levels. Our hypothesis was that mitochondrial function after T-H depends on SIRT1 activity. In this study, we evaluated the activity of SIRT1, a mitochondrial functional modulator, and the mitochondrial-glycolytic balance after T-H. We determined the changes in protein levels of pyruvate dehydrogenase kinase (PDK)-1 and nuclear c-Myc, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and NF-E2-related factor (NRF)2 after T-H and after treatment with resveratrol or a combination of sirtinol (a SIRT1 inhibitor) and resveratrol. We have also tested the activity of mitochondrial complex 1. SIRT1 enzyme activity was significantly decreased after T-H, whereas resveratrol treatment restored the activity. We found elevated PDK1 and c-Myc levels and decreased PGC-1α, NRF2 and mitochondrial complex I activity after T-H. The reduced SIRT1 activity after T-H may be related to declining mitochondrial function, since resveratrol was able to reinstate SIRT1 activity and mitochondrial function. The elevated level of PDK1 (an inhibitor of pyruvate dehydrogenase complex) after T-H indicates a possible shift in cellular energetics from mitochondria to glycolysis. In conclusion, SIRT1 modulation alters left ventricular function after T-H through regulation of cellular energetics.
- Molecular medicine (Cambridge, Mass.).Mol Med.2014 Mar 13;20:10-6. doi: 10.2119/molmed.2013.00077.
- Severe hemorrhage leads to decreased blood flow to tissues resulting in decreased oxygen and nutrient availability affecting mitochondrial function. A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline
- PMID 24395567
- Sensitization of metformin-cytotoxicity by dichloroacetate via reprogramming glucose metabolism in cancer cells.
- Choi YW1, Lim IK2.Author information 1Department of Biochemistry and Molecular Biology, BK21 Cell Transformation and Restoration Project, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.2Department of Biochemistry and Molecular Biology, BK21 Cell Transformation and Restoration Project, Ajou University School of Medicine, Suwon 443-721, Republic of Korea. Electronic address: iklim@ajou.ac.kr.AbstractTo investigate sensitization of metformin-cytotoxicity, cancer cells were treated with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK). Metformin-cytotoxicity was mainly dependent on glucose availability and reducing power generated by pentose phosphate pathway, whereas DCA cotreatment enhanced metformin-cytotoxicity via reprogramming glucose metabolism by inhibiting PDK and increasing mitochondrial respiration. DCA cotreatment elicited cell death rather than cell survival despite high glucose and high GSH condition. In conclusion, DCA sensitized metformin-cytotoxicity by reprogramming glucose metabolism in part from aerobic glycolysis to mitochondrial oxidation, evidenced by measurements of glucose consumption, lactate release, and the ratio of oxygen consumption rate/extracellular acidification rate.
- Cancer letters.Cancer Lett.2014 May 1;346(2):300-8. doi: 10.1016/j.canlet.2014.01.015. Epub 2014 Jan 27.
- To investigate sensitization of metformin-cytotoxicity, cancer cells were treated with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK). Metformin-cytotoxicity was mainly dependent on glucose availability and reducing power generated by pentose phosphate pathway, whereas DC
- PMID 24480191
- Metabolic alterations during the growth of tumour spheroids.
- Bloch K1, Smith H, van Hamel Parsons V, Gavaghan D, Kelly C, Fletcher A, Maini P, Callaghan R.Author information 1Doctoral Training Centre, University of Oxford, Rex Richards Building, Parks Road, Oxford, OX1 3QU, UK.AbstractSolid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms.
- Cell biochemistry and biophysics.Cell Biochem Biophys.2014 Apr;68(3):615-28. doi: 10.1007/s12013-013-9757-7.
- Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology
- PMID 24037715
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- Phosphoenol transphosphorylase. Phosphoenolpyruvate kinase. Reaction catalysed ATP + pyruvate => ADP + phosphoenolpyruvate Comment(s) UTP, GTP, CTP, ITP and dATP can also act as donors. Also phosphorylates 2.7 ...
★リンクテーブル★
[★]
- 英
- pyruvate kinase, PK
- 同
- ホスホエノールピルビン酸キナーゼ phosphoenolpyruvate kinase、ホスホエノールトランスホスホリラーゼ phosphoenol transphosphorylase
- 関
- 解糖系
- first aid step1 2006 p.87,89
ピルビン酸の生合成反応
CH2-C(OPO32-)-COOH + ADP + H+ －(ピルビン酸キナーゼ)→ CH3-CO-COO- + ATP
臨床関連
[★]
- 英
- phosphoenol transphosphorylase
- 関
- ピルビン酸キナーゼ