Differential contribution of pyruvate carboxylation to anaplerosis and cataplerosis during non-gluconeogenic and gluconeogenic conditions in HepG2 cells

Wattanavanitchakorn, Siriluck; Ansari, Israrul H.; Azzouny, Mahmoud El; Longacre, Melissa J.; Stoker, Scott W.; MacDonald, Michael J.; Jitrapakdee, Sarawut

doi:10.1016/j.abb.2019.108124

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…Pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) are crucial enzymes for gluconeogenesis in the liver [ 20 ]. PC catalyzes pyruvate carboxylation from oxaloacetate which converts to glucose by reversing the glycolytic pathway [ 28 ]. PEPCK directly catalyzes oxaloacetate to synthesize the phosphoenolpyruvate [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Gluconeogenesis Alteration and p53-SIRT6-Fox01 Signaling Adaptive Regulation in Sheep from Different Grazing Periods

Han

Chen

et al. 2022

Computational and Mathematical Methods in Medicine

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The decline in sheep health and meat quality caused by seasonal nutritional deficiencies has always been an important problem in the production of naturally grazing sheep. Glucose metabolism is crucial in ruminants for adequate cell function and maintenance of the body tissues and systems. However, whether glucose metabolism, especially gluconeogenesis, is affected by seasonal grazing conditions has not been fully uncovered. Thus, twelve sheep from two seasons (dry and green grass periods) in natural grazing areas of Inner Mongolia, China, were selected for this study. Their serum glucose, insulin, PC, and PEPCK levels and volatile fatty acid (gluconeogenesis material) concentrations in rumen fluid were analyzed. The expression of key enzymes including PC, PEPCK, GLUT2, and G6P of gluconeogenesis and their regulators INSR, PI3K/AKT and p53-SIRT6-Fox01 in the liver was detected by real-time PCR and western blotting. The results revealed significant variances in gluconeogenesis and its indicators and showed p53-SIRT6-Fox01 as having potential regulation in different grazing periods. This study offers new insights into the mechanism of gluconeogenesis and adaptive regulation between dry grass period and green grass period and also provides a reference for maintaining the health of sheep and meat quality despite seasonal nutritional deficiencies.

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Section: Discussionmentioning

confidence: 99%

Gluconeogenesis Alteration and p53-SIRT6-Fox01 Signaling Adaptive Regulation in Sheep from Different Grazing Periods

Han

Chen

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Tumor cells use glucose and glutamine to fuel anaplerosis and cell proliferation, which are catalyzed by pyruvate carboxylase and glutaminase respectively. Pyruvate carboxylase (PC) is the key anaplerotic enzyme that converts pyruvate to oxaloacetate in mitochondria, enabling the maintenance of other metabolic intermediates consumed by cataplerosis [25]. In glutamine-blocked tumor cells, the induction of a compensatory anaplerotic mechanism catalyzed by PC, allowed the cells to use glucose-derived pyruvate rather than glutamine for anaplerosis [3].…”

Section: Discussionmentioning

confidence: 99%

NDRG2 Inhibits Pyruvate Carboxylase-Mediated Anaplerosis and Combines with Glutamine Blockade To Inhibit The Growth of Glioma

Wang

Sun

Wang

et al. 2021

Preprint

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Background Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of the tumor suppressor NDRG2 in PC and PC-mediated anaplerosis. Methods We first evaluated the correlation between PC and NDRG2 in glioma cell lines and human glioma tissue microarrays. The interaction between PC and NDRG2 was tested by tandem affinity purification-mass spectrometry (TAP-MS) and coimmunoprecipitation (Co-IP). We then detected the effect of NDRG2 on PC-mediated anaplerosis by gas chromatography-mass spectrometry (GC-MS). Preclinical evaluation of NDRG2 alone or combined with a glutaminase inhibitor was conducted in glioma cells and xenograft mouse tumors. Results NDRG2 interacted with PC and induced the degradation of PC in glutamine-deficient glioma cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in IDH1(R132H)-mutant glioma cells than in wild-type glioma cells. Conclusions These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.

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“…For example, anaplerotic enzyme pyruvate carboxylase which catalyzes pyruvate carboxylation to support anaplerosis by supplying oxaloacetate to TCA cycle. Suppression of pyruvate carboxylase decreases the flux of TCA cycle intermediates, aspartate, glutamate and glucose derivatives, which in turn reduces the viability and proliferation of HCC HepG2 cells 64 .…”

Section: Metabolic Rearrangements In Hccmentioning

confidence: 99%

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Liu

Qin

et al. 2022

Acta Pharmaceutica Sinica B

292

155

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Differential contribution of pyruvate carboxylation to anaplerosis and cataplerosis during non-gluconeogenic and gluconeogenic conditions in HepG2 cells

Cited by 7 publications

References 33 publications

Gluconeogenesis Alteration and p53-SIRT6-Fox01 Signaling Adaptive Regulation in Sheep from Different Grazing Periods

Gluconeogenesis Alteration and p53-SIRT6-Fox01 Signaling Adaptive Regulation in Sheep from Different Grazing Periods

NDRG2 Inhibits Pyruvate Carboxylase-Mediated Anaplerosis and Combines with Glutamine Blockade To Inhibit The Growth of Glioma

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

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