scholarly journals Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Simranjot Bawa ◽  
David S Brooks ◽  
Kathryn E Neville ◽  
Marla Tipping ◽  
Md Abdul Sagar ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Model ◽  
Wing Disc ◽  
Glycolytic Enzymes ◽  
Phosphoglycerate Mutase ◽  
Glycolytic Flux ◽  
Amino Acid Supplementation ◽  
Glycolytic Metabolism ◽  
Glycolytic Intermediates ◽  
Dietary Amino Acid

Cell growth and/or proliferation may require the reprogramming of metabolic pathways, whereby a switch from oxidative to glycolytic metabolism diverts glycolytic intermediates towards anabolic pathways. Herein, we identify a novel role for TRIM32 in the maintenance of glycolytic flux mediated by biochemical interactions with the glycolytic enzymes Aldolase and Phosphoglycerate mutase. Loss of Drosophila TRIM32, encoded by thin (tn), shows reduced levels of glycolytic intermediates and amino acids. This altered metabolic profile correlates with a reduction in the size of glycolytic larval muscle and brain tissue. Consistent with a role for metabolic intermediates in glycolysis-driven biomass production, dietary amino acid supplementation in tn mutants improves muscle mass. Remarkably, TRIM32 is also required for ectopic growth - loss of TRIM32 in a wing disc-associated tumor model reduces glycolytic metabolism and restricts growth. Overall, our results reveal a novel role for TRIM32 for controlling glycolysis in the context of both normal development and tumor growth.

Glycolytic regulation during an aerobic rest-to-work transition in dog gracilis muscle

1987 ◽  
Vol 63 (6) ◽  
pp. 2366-2374 ◽  
Author(s):  
R. J. Connett
Keyword(s):  
Glycogen Phosphorylase ◽  
Gracilis Muscle ◽  
Phosphoglycerate Mutase ◽  
Glycolytic Flux ◽  
Cytosolic Ph ◽  
Initial Burst ◽  
Work Transition ◽  
Glycolytic Intermediates ◽  
Glycogen Phosphorylase Activity ◽  
Rate Limiting

Glycogen phosphorylase activity and several glycolytic intermediates were measured at rest and after 5, 10, 15, 30, 60, and 180 s of twitch stimulation at 4 Hz in fast-frozen samples of gracilis muscle. During an initial burst of glycolysis (0–5 s) only 3-phosphoglycerate and lactate accumulate. These changes are reversed during the period of low glycolytic flux (5–30 s). During a second burst of glycolysis (30–60 s) most glycolytic intermediates increase. The levels of glycogen phosphorylase a changes in parallel with the initial burst of glycolysis but remain at resting levels throughout the second burst. The phosphoglycerate mutase-enolase steps deviate from equilibrium during the initial burst of glycolysis, suggesting a transiently rate-limiting role. Analysis using a model of phosphofructokinase kinetics indicates that combined changes in cytosolic pH (R. J. Connett, J. Appl. Physiol. 63: 2360–2365, 1987) and free [ADP] and [AMP] can account for the initial burst of glycolysis. The second burst of glycolysis requires other regulatory factors. It is concluded that an initial alkalization is a major regulatory factor in the early burst of glycolysis during a rest-to-work transition in red muscle.

scholarly journals Introductory remarks to the third session

1981 ◽  
Vol 293 (1063) ◽  
pp. 119-119
Keyword(s):  
Active Site ◽  
Glycolytic Enzymes ◽  
Striking Feature ◽  
Phosphoglycerate Mutase ◽  
Personal Interest ◽  
The Third ◽  
Set Up

This session is of particular personal interest to me. Almost exactly four years ago I completed the manuscript of my book with a section on glycolytic enzymes. At that time, some very interesting and tantalizing results were emerging from the crystallographic laboratories in Bristol and Oxford, so I paid visits to Dr Watson and Dr Muirhead and Professor Phillips with the result that I was able to include some speculative, unpublished, ideas on mechanism. It is now most intriguing to see the progress since 1976 and how some early speculations have held up or developed. The first speakers in this session, Dr Watson and Dr Fothergill, had just found a most striking feature at the active site of phosphoglycerate mutase: the two imidazole rings of the active site histidines are parallel and only 4 A apart, apparently well set up for shuffling the phosphate between 2-phosphoglycerate and 3-phosphoglycerate via two phosphoenzyme intermediates. I see from the abstract that subsequent data conflict with this idea.

scholarly journals Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes

2015 ◽  
Vol 109 (3) ◽  
pp. 397-408 ◽  
Author(s):  
Nahuel A. Garcia ◽  
Javier Moncayo-Arlandi ◽  
Pilar Sepulveda ◽  
Antonio Diez-Juan
Keyword(s):  
Glycolytic Enzymes ◽  
Glycolytic Flux ◽  
Direct Transfer

scholarly journals Inhibition of glycolytic enzymes by 2-phosphotartronate

1976 ◽  
Vol 153 (3) ◽  
pp. 741-744 ◽  
Author(s):  
M K Thomas ◽  
T G Spring
Keyword(s):  
Pyruvate Kinase ◽  
Competitive Inhibition ◽  
Phosphoglycerate Kinase ◽  
Triose Phosphate Isomerase ◽  
Glycolytic Enzymes ◽  
Phosphoglycerate Mutase ◽  
Rabbit Muscle ◽  
Triose Phosphate ◽  
Permanganate Oxidation

2-Phosphotartronate has been synthesized by permanganate oxidation of glycerol 2-phosphate and has been tested as an inhibitor of five glycolytic enzymes that bind phosphoglycerate or phosphoglycollate. Competitive inhibition of rabbit muscle phosphoglycerate mutase, enolase and pyruvate kinase was observed. Triose phosphate isomerase and 3-phosphoglycerate kinase were not inhibited.

The role of phosphoglycerate mutase 2 in UM-UC3 bladder cancer cell metabolism.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 410-410
Author(s):  
Ryan Didde ◽  
Weiya Liu ◽  
Karim Pirani ◽  
Gaurav Kaushik ◽  
Benjamin L. Woolbright ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Differential Expression ◽  
Control Cell ◽  
Phosphoglycerate Mutase ◽  
Patients With Diabetes ◽  
Automated Cell Counter ◽  
Cell Counter

410 Background: Bladder cancer remains the fourth most common cancer in American males with a higher risk of recurrence and progression for patients with diabetes mellitus. Urothelial bladder cancer is characterized by aerobic glycolysis with upregulation of glycolytic enzymes (known as the Warburg effect) such as phosphoglycerate mutase. Phosphoglycerate mutase 2 (PGAM2), a reversible glycolytic enzyme expressed highly in muscle, represents a target for modulation because of its differential expression from another isoform, phosphoglycerate mutase 1. PGAM2 knockdown may impact bladder cancer growth significantly via its effect on glucose metabolism at different glucose concentrations seen in patients with diabetes mellitus. Methods: UM-UC3 bladder cancer cells were assessed for PGAM2 expression at different glucose concentrations via Western blot and quantitative PCR. One native UM-UC3 line, three PGAM2 knockdown lines, and one vector control cell line were included in the western blot study. Cellular proliferation was analyzed using an enzyme based hexoseaminidase assay and was further supported with an automated cell counter. The effects of cisplatin were also investigated. Results: Increased PGAM2 expression at increased glucose concentrations in UM-UC3 was confirmed by Western blot and quantitative PCR. PGAM2 knockdown cells responded differently to changes in glucose concentration compared to the control cell lines, with a large increase in growth at a low glucose level of 25mg/dL after day 4. Cell proliferation demonstrated similar growth between the knockdown and controls at higher glucose concentrations of 100 and 200mg/dL. Proliferation data using automated cell counter demonstrate the same growth trend. Conclusions: Increased cell growth of PGAM2 knockdowns, most notably at 25mg/dL, suggests that PGAM2 may play a different role in glycolysis than expected, possibly serving as a modulator in cell growth instead of a simple reversible enzyme. We are currently investigating its differential expression compared to PGAM1, an enzyme recently characterized to have an opposite effect to PGAM2.

scholarly journals Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption

2018 ◽  
Vol 314 (3) ◽  
pp. E214-E223 ◽  
Author(s):  
Sally Winther ◽  
Marie S. Isidor ◽  
Astrid L. Basse ◽  
Nina Skjoldborg ◽  
Amanda Cheung ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Glucose Consumption ◽  
Glucose Transporters ◽  
Glycolytic Enzymes ◽  
Brown Adipocyte ◽  
Glycolytic Flux ◽  
Acid Oxidation ◽  
Cold Stimulation ◽  
Brown Adipocytes ◽  
Effect Of Glucose

During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation. Knockdown of glucose transporters in brown adipocytes not only impaired ISO-stimulated glycolytic flux but also oxygen consumption. Diminishing glycolytic flux by knockdown of the first and final enzyme of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways.

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