A New Role of Phosphoglucose Isomerase. Involvement of the Glycolytic Enzyme in Aldehyde Metabolism

2005 ◽  
Vol 70 (11) ◽  
pp. 1251-1255 ◽  
Author(s):  
Z. S. Agadjanyan ◽  
L. F. Dmitriev ◽  
S. F. Dugin
Keyword(s):  
Glycolytic Enzyme ◽  
Phosphoglucose Isomerase

scholarly journals Metabolic modulation regulates cardiac wall morphogenesis in zebrafish

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ryuichi Fukuda ◽  
Alla Aharonov ◽  
Yu Ting Ong ◽  
Oliver A Stone ◽  
Mohamed El-Brolosy ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Glycolytic Enzyme ◽  
Form Complex ◽  
Neonatal Cardiomyocytes ◽  
Cardiac Wall ◽  
Wall Structures ◽  
Resolution Imaging ◽  
Inhibition Of Glycolysis ◽  
And Behavior

During cardiac development, cardiomyocytes form complex inner wall structures called trabeculae. Despite significant investigation into this process, the potential role of metabolism has not been addressed. Using single cell resolution imaging in zebrafish, we find that cardiomyocytes seeding the trabecular layer actively change their shape while compact layer cardiomyocytes remain static. We show that Erbb2 signaling, which is required for trabeculation, activates glycolysis to support changes in cardiomyocyte shape and behavior. Pharmacological inhibition of glycolysis impairs cardiac trabeculation, and cardiomyocyte-specific loss- and gain-of-function manipulations of glycolysis decrease and increase trabeculation, respectively. In addition, loss of the glycolytic enzyme pyruvate kinase M2 impairs trabeculation. Experiments with rat neonatal cardiomyocytes in culture further support these observations. Our findings reveal new roles for glycolysis in regulating cardiomyocyte behavior during cardiac wall morphogenesis.

scholarly journals Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation

2018 ◽  
Author(s):  
Jamie A. Macpherson ◽  
Alina Theisen ◽  
Laura Masino ◽  
Louise Fets ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
High Activity ◽  
Pyruvate Kinase ◽  
Cross Talk ◽  
Glycolytic Enzyme ◽  
Computational Framework ◽  
Allosteric Inhibitor ◽  
Fructose 1,6 Bisphosphate ◽  
Low Activity

ABSTRACTAllosteric regulation is central to the role of the glycolytic enzyme pyruvate kinase M2 (PKM2) in cellular metabolism. Multiple activating and inhibitory allosteric ligands regulate PKM2 activity by controlling the equilibrium between high activity tetramers and low activity dimers and monomers. However, it remains elusive how allosteric inputs upon simultaneous binding of different ligands are integrated to regulate PKM2 activity. Here, we show that, in the presence of the allosteric inhibitor L-phenylalanine (Phe), the activator fructose 1,6-bisphosphate (FBP) can induce PKM2 tetramerisation, but fails to maximally increase enzymatic activity. Guided by a new computational framework we developed to identify residues that mediate FBP-induced allostery, we generated two PKM2 mutants, A327S and C358A, in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings demonstrate a role for residues involved in FBP-induced allostery in enabling the integration of allosteric input from Phe and reveal a mechanism that underlies the co-ordinate regulation of PKM2 activity by multiple allosteric ligands.

scholarly journals SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions

2016 ◽  
Vol 113 (5) ◽  
pp. E538-E547 ◽  
Author(s):  
Abhishek Bhardwaj ◽  
Sanjeev Das
Keyword(s):  
Tumor Suppressor ◽  
Nuclear Export ◽  
Genome Stability ◽  
Nuclear Protein ◽  
Glycolytic Enzyme ◽  
Mouse Tumor ◽  
Transcriptional Coactivator ◽  
Migration Potential ◽  
Mouse Tumor Models

SIRT6 (sirtuin 6) is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis, and tumorigenesis. However, the role of SIRT6 deacetylase activity in its tumor-suppressor functions is not well understood. Here we report that SIRT6 binds to and deacetylates nuclear PKM2 (pyruvate kinase M2) at the lysine 433 residue. PKM2 is a glycolytic enzyme with nonmetabolic nuclear oncogenic functions. SIRT6-mediated deacetylation results in PKM2 nuclear export. We further have identified exportin 4 as the specific transporter mediating PKM2 nuclear export. As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus, SIRT6 suppresses PKM2 oncogenic functions, resulting in reduced cell proliferation, migration potential, and invasiveness. Furthermore, studies in mouse tumor models demonstrate that PKM2 deacetylation is integral to SIRT6-mediated tumor suppression and inhibition of metastasis. Additionally, reduced SIRT6 levels correlate with elevated nuclear acetylated PKM2 levels in increasing grades of hepatocellular carcinoma. These findings provide key insights into the pivotal role of deacetylase activity in SIRT6 tumor-suppressor functions.

scholarly journals Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Keqiu Jiang ◽  
Chengyong Dong ◽  
Zeli Yin ◽  
Rui Li ◽  
Jiakai Mao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Glycolytic Enzyme ◽  
Tumor Node Metastasis ◽  
Patient Deterioration ◽  
Node Metastasis ◽  
Integrin Α6β4 ◽  
P38mapk Pathway ◽  
Metastatic Risk ◽  
Hcc Cells

Abstract Alpha-enolase (ENO1) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). Although the role of ENO1 as a glycolytic enzyme in HCC cells has been well characterized, little is known about the other roles of ENO1, especially exosome-derived ENO1, in regulating HCC progression. Here, we demonstrated that ENO1 is frequently upregulated in HCC cells or tissues, with even higher expression in highly metastatic HCC cells or metastatic tissues as well as in exosomes derived from highly metastatic sources. Moreover, ENO1 expression is associated with the tumor-node-metastasis (TNM) stage, differentiation grade and poor prognosis in HCC patients. Surprisingly, ENO1 can be transferred between HCC cells via exosome-mediated crosstalk, exhibiting an effect similar to that of ENO1 overexpression in HCC cells, which promoted the growth and metastasis of HCC cells with low ENO1 expression by upregulating integrin α6β4 expression and activating the FAK/Src-p38MAPK pathway. In summary, our data suggest that exosome-derived ENO1 is essential to promoting HCC growth, metastasis, and further patient deterioration. The findings from this study implicate a novel biomarker for the clinical evaluation of HCC progression, especially the prediction of HCC metastatic risk.

Insulin protects acinar cells during cellular and animal models of acute pancreatitis: Role of Akt-mediated phosphorylation of the glycolytic enzyme PFKFB2

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S101-S102
Author(s):  
Rosa Sanchez-Alvarez ◽  
Sarah Sudgen ◽  
M Dolors Sans ◽  
John A. Williams ◽  
Jason I.E. Bruce
Keyword(s):  
Acute Pancreatitis ◽  
Animal Models ◽  
Acinar Cells ◽  
Glycolytic Enzyme

Genome-wide analysis of Kluyveromyces lactis in wild-type and rag2 mutant strains

Genome ◽  
2004 ◽  
Vol 47 (5) ◽  
pp. 970-978 ◽  
Author(s):  
Manuel Becerra ◽  
Nuria Tarrío ◽  
M Isabel González-Siso ◽  
M Esperanza Cerdán
Keyword(s):  
Kluyveromyces Lactis ◽  
Glycolytic Enzyme ◽  
Pentose Phosphate ◽  
Phosphoglucose Isomerase ◽  
Transcriptional Level ◽  
Dna Arrays ◽  
Gene Coding ◽  
Genome Wide ◽  
Rag2 Gene ◽  
Interesting Alternative

The use of heterologous DNA arrays from Saccharomyces cerevisiae has been tested and revealed as a suitable tool to compare the transcriptomes of S. cerevisiae and Kluyveromyces lactis, two yeasts with notable differences in their respirofermentative metabolism. The arrays have also been applied to study the changes in the K. lactis transcriptome owing to mutation in the RAG2 gene coding for the glycolytic enzyme phosphoglucose isomerase. Comparison of the rag2 mutant growing in 2% glucose versus 2% fructose has been used as a model to elucidate the importance of transcriptional regulation of metabolic routes, which may be used to reoxidize the NADPH produced in the pentose phosphate pathway. At this transcriptional level, routes related to the oxidative stress response become an interesting alternative for NADPH use.Key words: Kluyveromyces lactis, transcription, phosphoglucose isomerase, carbohydrate use.

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