Alternative Binding of Two Sequential Glycolytic Enzymes to Microtubules

Vértessy, Beáta G.; Orosz, Ferenc; Kovács, János; Ovádi, Judit

doi:10.1074/jbc.272.41.25542

Cited by 73 publications

(35 citation statements)

References 30 publications

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“…Several metabolic enzymes, including hexokinase, aldolase, PFK, GAPDH, and PK, bind to microfilaments and/or microtubules (23,(42)(43)(44)(45)(46)(47). These interactions can alter both metabolic activity and cytoskeletal properties.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils

Kindzelskii¹,

Huang²,

Chaiworapongsa³

et al. 2002

J. Clin. Invest.

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Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO2 indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils

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Section: Discussionmentioning

confidence: 99%

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils

Kindzelskii¹,

Huang²,

Chaiworapongsa³

et al. 2002

J. Clin. Invest.

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“…Some of the latter contradictory results could reflect differences in experimental methods or purity of enzyme components. Indeed, analysis of two sequential enzymes, PFK and aldolase, and their regulation by MT binding, demonstrates that a complex formed by the two enzymes no longer associates with MTs [Vertessy et al, 1997]. In some cases, e.g., aldolase [Vertessy et al, 1997], MT binding competes with substrate for enzyme binding and therefore MTs can act as a competitive inhibitor to reduce enzyme activity in these situations.…”

Section: Cytoskeletonmentioning

confidence: 99%

“…The remaining enzymes have either not been tested (PGK) or their activities are unaltered by MT binding (enolase [Keller et al, 2007]). Enzymes showing reduced activity when bound to MTs are PFK (muscle isoform [Lehotzky et al, 1993;Vertessy et al, 1997]) and TPI [Orosz et al, 2000]. Enzymes with greater activity when bound to MTs include HK [Wagner et al, 2001] and PK [Walsh et al, 1989].…”

mentioning

confidence: 99%

“…Indeed, analysis of two sequential enzymes, PFK and aldolase, and their regulation by MT binding, demonstrates that a complex formed by the two enzymes no longer associates with MTs [Vertessy et al, 1997]. In some cases, e.g., aldolase [Vertessy et al, 1997], MT binding competes with substrate for enzyme binding and therefore MTs can act as a competitive inhibitor to reduce enzyme activity in these situations.Binding of enzymes, which act in series, to a solid support (e.g., MTs) has been proposed to facilitate enzymatic reactions by providing a scaffold to organize enzymes sequentially [Srere, 1987]. For example, purine biosynthesis occurs in clusters bound to MTs, which increases the rate of purine synthesis .…”

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confidence: 99%

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Fueled by microtubules: Does tubulin dimer/polymer partitioning regulate intracellular metabolism?

et al. 2012

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Microtubules (MTs) or their subunits, tubulin dimers, interact with multiple components that contribute to intracellular metabolic pathways. MTs are required for insulin-dependent transport of glucose transporter 4 to the plasma membrane, they bind most glycolytic enzymes and are required for translation of the mRNA encoding hypoxia inducible factor-1a. Tubulin dimers bind the voltage-dependent anion channel of the mitochondrial outer membrane; this channel functions in metabolite transport in and out of mitochondria. We hypothesize that tubulin partitioning between dimer and polymer pools regulates multiple steps in metabolism, where metabolic output is greatest when both tubulin dimers and MT polymers are present and reduced by drug treatments that disrupt this normal balance. Experimental evidence from these drug-induced changes in tubulin dimer/polymer partitioning supports our model for several metabolic steps. Signal transduction pathways that stabilize or destabilize MTs can shift the normal ratio between unpolymerized and polymerized tubulin dimers, and one downstream consequence of this shift in tubulin partitioning could be a change in metabolic output. V C 2012 Wiley Periodicals, Inc Key Words: glycolysis, oxidative phosphorylation, glucose transport, voltage-dependent anion channel, tubulin IntroductionT he microtubule (MT) cytoskeleton has well-characterized roles in cell polarity, motility, mitosis, and vesicle traffic. The dynamic turnover of MTs is critical to most of these processes, allowing the cell to reorganize an array of MTs rapidly for specific functions. Here we posit an additional role for MTs in regulating metabolic processes and propose that metabolism is greatest when both MTs and their tubulin subunits are present in cells. Disruption of this normal balance, to either inhibit or promote MT polymerization, is expected to decrease metabolic output. Our hypothesis predicts that chemotherapies that stabilize or destabilize MTs will significantly impact metabolic pathways and reduce ATP levels. Importantly, even a small decrease in ATP production can slow cell proliferation. For example, a 19% decrease in ATP production was sufficient to induce senescence in mouse embryo fibroblasts [Kondoh et al., 2005], indicating that even a relatively small contribution of the MT cytoskeleton to metabolic output could have a significant impact on cell fate.The metabolic components and pathways we consider here include glucose transporters (GLUTs), glycolysis, the pentose phosphate pathway (PPP), and mitochondrial oxidative phosphorylation. Glucose enters cells through glucose transporters called GLUTs; the concentration of GLUTs at the plasma membrane can be regulated by insulin and requires trafficking of GLUT-containing vesicles along MTs to reach the plasma membrane. Within the cytoplasm, glucose is broken down to pyruvate during glycolysis, yielding ATP and NADH. Several intermediate products of glucose breakdown, including glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate (GAP), can also ...

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“…Several experimental evidence noted how this enzyme plays a key role in the mechanisms involved in cellular motility, 17,18 interacts with microtubules and has a potential role in the regulation of energy metabolism. 19,20 The association of glycolytic enzymes, including alpha-enolase, seems to be important for human sperm motility. 17 For example it has been demonstrated that the high amount of ATP required in Chlamydomonas for flagella motility is supported by the presence of enolase in the flagellar microtubular compartment.…”

Section: View Article Onlinementioning

confidence: 99%

Unravelling the bull fertility proteome

et al. 2013

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In the last few decades a negative association between the level of milk production and fertility has been observed. Currently, the most utilized method of measuring male fertility employed by the livestock industry is related to the Non-Return Rate (NRR). Through differential proteome analysis, this study evaluated changes in the expression of the protein profile of spermatozoa collected from 16 bulls with different levels of field fertility expressed as an estimated relative conception rate (ERCR). The main aim is to identify putative protein markers to be used as putative indices of fertility. Two dimensional electrophoresis coupled with mass spectrometry analysis was used for protein separation and identification. To improve differential proteome analysis among experimental groups, a part of shotgun MS analysis was also performed. Three protein spots showed a differential expression pattern among all ERCR classes. Alpha enolase was significantly down-regulated in the ERCRÀ group, while two other proteins, isocitrate dehydrogenase and triosephosphate isomerase, were up-regulated in ERCRÀ in comparison to ERCR+. Alpha-enolase and isocitrate dehydrogenase subunit alpha (IDH-alpha) have been described in the literature for having a potential role in bull fertility. The possibility of determining protein biomarkers for fertility is more useful and less expensive than ERCR for acquiring rapid estimation of fertility because it does not require the use of field insemination trials. Shotgun MS analysis conducted on the same samples revealed 7 proteins down-regulated in the ERCRÀ group and 1 protein up-regulated. Among these proteins, calmodulin, ATP synthase mitochondrial subunits alpha and delta, malate dehydrogenase and sperm equatorial segment protein 1 were shown to be linked with sperm fertility.

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Alternative Binding of Two Sequential Glycolytic Enzymes to Microtubules

Cited by 73 publications

References 30 publications

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils

Fueled by microtubules: Does tubulin dimer/polymer partitioning regulate intracellular metabolism?

Unravelling the bull fertility proteome

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