scholarly journals From Glucose to Lactate and Transiting Intermediates Through Mitochondria, Bypassing Pyruvate Kinase: Considerations for Cells Exhibiting Dimeric PKM2 or Otherwise Inhibited Kinase Activity

2020 ◽  
Vol 11 ◽  
Author(s):  
Christos Chinopoulos
Keyword(s):  
Oxidative Phosphorylation ◽  
Pyruvate Kinase ◽  
Posttranslational Modifications ◽  
Cancer Metabolism ◽  
Kinase Activity ◽  
Nitrosative Stress ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Mitochondrial Matrix ◽  
Pyruvate Kinase Activity

A metabolic hallmark of many cancers is the increase in glucose consumption coupled to excessive lactate production. Mindful that L-lactate originates only from pyruvate, the question arises as to how can this be sustained in those tissues where pyruvate kinase activity is reduced due to dimerization of PKM2 isoform or inhibited by oxidative/nitrosative stress, posttranslational modifications or mutations, all widely reported findings in the very same cells. Hereby 17 pathways connecting glucose to lactate bypassing pyruvate kinase are reviewed, some of which transit through the mitochondrial matrix. An additional 69 converging pathways leading to pyruvate and lactate, but not commencing from glucose, are also examined. The minor production of pyruvate and lactate by glutaminolysis is scrutinized separately. The present review aims to highlight the ways through which L-lactate can still be produced from pyruvate using carbon atoms originating from glucose or other substrates in cells with kinetically impaired pyruvate kinase and underscore the importance of mitochondria in cancer metabolism irrespective of oxidative phosphorylation.

scholarly journals Insulin Regulates Glucose Consumption and Lactate Production through Reactive Oxygen Species and Pyruvate Kinase M2

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qi Li ◽  
Xue Liu ◽  
Yu Yin ◽  
Ji-Tai Zheng ◽  
Cheng-Fei Jiang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Cancer ◽  
Pyruvate Kinase ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Lactate Production ◽  
Reactive Oxygen ◽  
Glucose Consumption ◽  
Oxygen Species ◽  
Pyruvate Kinase M2

Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2) expression through reactive oxygen species (ROS) for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer cell growth and insulin-induced glucose consumption and lactate production, suggesting that PKM2 is a functional downstream effecter of insulin. Taken together, this study would provide a new insight into the mechanism of insulin-induced glycolysis.

Red blood cell age, pyruvate kinase activity, and insulin receptors. Evidence that monocytes and RBCs may behave differently

Diabetes ◽  
1983 ◽  
Vol 32 (11) ◽  
pp. 1017-1022 ◽  
Author(s):  
A. Camagna ◽  
R. De Pirro ◽  
L. Tardella ◽  
L. Rossetti ◽  
R. Lauro ◽  
...  
Keyword(s):  
Blood Cell ◽  
Pyruvate Kinase ◽  
Red Blood Cell ◽  
Kinase Activity ◽  
Insulin Receptors ◽  
Pyruvate Kinase Activity ◽  
Cell Age

Red Blood Cell Age, Pyruvate Kinase Activity, and Insulin Receptors: Evidence that Monocytes and RBCs May Behave Differently

Diabetes ◽  
1983 ◽  
Vol 32 (11) ◽  
pp. 1017-1022 ◽  
Author(s):  
A. Camagna ◽  
R. D. Pirro ◽  
L. Tardella ◽  
L. Rossetti ◽  
R. Lauro ◽  
...  
Keyword(s):  
Blood Cell ◽  
Pyruvate Kinase ◽  
Red Blood Cell ◽  
Kinase Activity ◽  
Insulin Receptors ◽  
Pyruvate Kinase Activity ◽  
Cell Age

Pyruvate kinase activity in cerebral hemispheres and cerebellum-brainstem of normal and hypoxic-ischemic newborn rats

2004 ◽  
Vol 3 (3) ◽  
pp. 152-155 ◽  
Author(s):  
Hacer Yapicioglu ◽  
Mehmet Satar ◽  
Nejat Narli ◽  
Levent Kayrin ◽  
Ercan Tutak
Keyword(s):  
Pyruvate Kinase ◽  
Kinase Activity ◽  
Cerebral Hemispheres ◽  
Newborn Rats ◽  
Pyruvate Kinase Activity

scholarly journals Central metabolism of functionally heterogeneous mesenchymal stromal cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mario Barilani ◽  
Roberta Palorini ◽  
Giuseppina Votta ◽  
Roberta Piras ◽  
Giuseppe Buono ◽  
...  
Keyword(s):  
Stem Cells ◽  
Oxidative Phosphorylation ◽  
Cell Fate ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Mitochondrial Activity ◽  
Central Metabolism ◽  
Mt Dna ◽  
Differentiation Potential ◽  
And Function

Abstract Metabolism and mitochondrial biology have gained a prominent role as determinants of stem cell fate and function. In the context of regenerative medicine, innovative parameters predictive of therapeutic efficacy could be drawn from the association of metabolic or mitochondrial parameters to different degrees of stemness and differentiation potentials. Herein, this possibility was addressed in human mesenchymal stromal/stem cells (hMSC) previously shown to differ in lifespan and telomere length. First, these hMSC were shown to possess significantly distinct proliferation rate, senescence status and differentiation capacity. More potential hMSC were associated to higher mitochondrial (mt) DNA copy number and lower mtDNA methylation. In addition, they showed higher expression levels of oxidative phosphorylation subunits. Consistently, they exhibited higher coupled oxygen consumption rate and lower transcription of glycolysis-related genes, glucose consumption and lactate production. All these data pointed at oxidative phosphorylation-based central metabolism as a feature of higher stemness-associated hMSC phenotypes. Consistently, reduction of mitochondrial activity by complex I and III inhibitors in higher stemness-associated hMSC triggered senescence. Finally, functionally higher stemness-associated hMSC showed metabolic plasticity when challenged by glucose or glutamine shortage, which mimic bioenergetics switches that hMSC must undergo after transplantation or during self-renewal and differentiation. Altogether, these results hint at metabolic and mitochondrial parameters that could be implemented to identify stem cells endowed with superior growth and differentiation potential.

Superoxide dismutase and cytochrome oxidase in collapsed lungs: possible role in reexpansion edema

1988 ◽  
Vol 65 (1) ◽  
pp. 235-241 ◽  
Author(s):  
R. M. Jackson ◽  
A. L. Brannen ◽  
C. F. Veal ◽  
J. D. Fulmer
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome Oxidase ◽  
Pyruvate Kinase ◽  
Kinase Activity ◽  
H2o2 Production ◽  
Lung Collapse ◽  
Pyruvate Kinase Activity ◽  
Sod Activity ◽  
Control Rabbit ◽  
Radical Production

This study examined the effects of lung collapse, a condition that causes relative hypoxia in lung tissues, on superoxide dismutase (SOD), cytochrome oxidase (cyt ox), and pyruvate kinase (py ki) activities in rabbits. Cyanide-insensitive respiration measurements were done in collapsed and contralateral lungs, as an index of intracellular free radical production. Rabbits' right lungs were collapsed for 7 days after which the animals were killed. We found that control rabbit lungs contained approximately 25 SOD units/mg DNA measured with 10(-5) M KCN (total SOD) and approximately 11 SOD units/mg DNA measured with 10(-3) M KCN (mitochondrial or MnSOD). Right lung collapse caused a 25% decrease in mitochondrial SOD activity after 7 days (P less than 0.05), whereas no significant changes occurred in right or left lungs' total SOD activity. In control rabbits cyt ox activity averaged approximately 0.009 mumol ferrocytochrome c.min-1.mg DNA-1. Right lung collapse caused a greater than 40% decrease in cyt ox activity after 7 days of collapse (P less than 0.05), whereas cyt ox activity in contralateral left lungs did not change. Pyruvate kinase activity, a marker for anaerobic glycolysis resulting from tissue hypoxia, increased 49% in collapsed right lungs (P less than 0.01). Cyanide-insensitive respiration was 83% higher in 7 day-collapsed lungs (2.28 +/- 0.66 microliters O2.min-1.g-1) compared with contralateral lungs (1.24 +/- 0.34, P less than 0.05), indicating increased O2-. and H2O2 production in this tissue after homogenization at normoxic PO2 (approximately 150 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)

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