Topic
Pyruvate kinase
About: Pyruvate kinase is a research topic. Over the lifetime, 5683 publications have been published within this topic receiving 180020 citations. The topic is also known as: ATP:pyruvate 2-O-phosphotransferase & phosphoenolpyruvate kinase.
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TL;DR: It is suggested that GCs prevent tumor cells from generating the energy needed to repair membrane damage, fatty acid oxidation is a mechanism of resistance to GC-mediated cytotoxicity, and PPARα inhibition is a strategy to improve the therapeutic efficacy of GCs.
75 citations
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TL;DR: The proteomic analysis of aged muscle has identified a large cohort of new biomarkers of sarcopenia including opposite changes in PK and AK, which might be useful for the design of improved diagnostic procedures and/or therapeutic strategies to counteract ageing‐induced muscle degeneration.
Abstract: Sarcopenia is the drastic loss of skeletal muscle mass and strength during ageing. In order to better understand the molecular pathogenesis of age-related muscle wasting, we have performed a DIGE analysis of young adult versus old rat skeletal muscle. Proteomic profiling revealed that out of 2493 separated 2-D spots, 69 proteins exhibited a drastically changed expression. Age-dependent alterations in protein abundance indicated dramatic changes in metabolism, contractile activity, myofibrillar remodelling and stress response. In contrast to decreased levels of pyruvate kinase (PK), enolase and phosphofructokinase, the mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and adenylate kinase (AK) were increased in senescent fibres. Higher expression levels of myoglobin and fatty acid binding-protein indicated a shift to more aerobic-oxidative metabolism in a slower-twitching aged fibre population. The drastic increase in alphaB-crystallin and myotilin demonstrated substantial filament remodelling during ageing. An immunoblotting survey of selected muscle proteins confirmed the pathobiochemical transition process in aged muscle metabolism. The proteomic analysis of aged muscle has identified a large cohort of new biomarkers of sarcopenia including opposite changes in PK and AK, which might be useful for the design of improved diagnostic procedures and/or therapeutic strategies to counteract ageing-induced muscle degeneration.
75 citations
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TL;DR: Oral vanadate given to diabetic rats induces a shift of the predominating gluconeogenic flux, with subsequent high hepatic glucose production, into a glycolytic flux by pretranslational regulatory mechanisms.
74 citations
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TL;DR: The total specific pyruvate kinase activity and the amount of the tumour type M2-PK measured by ELISA was increased in the tumor samples compared to the normal colon mucosa of the same patient and showed a highly significant difference.
Abstract: Proliferating and tumor cells express a certain isoenzyme of pyruvate kinase, called PK type M2. This isoenzyme can be isolated in an active tetrameric and an inactive dimeric form. We have termed this form tumor type M2-PK. This tumor type pyruvate kinase can be quantified by a specific ELISA in blood sera and tumor homogenates. In this study we have compared 26 normal colon mucosa and colon cancer specimens from the same patients. The total specific pyruvate kinase activity and the amount of the tumour type M2-PK measured by ELISA was increased in the tumor samples compared to the normal colon mucosa of the same patient. In normal colon mucosa the specific PK-activity ranged between 0.21 and 1.25 U/mg protein whereas in colon carcinoma we found activities between 0.99 and 7.08 U/mg. The amount of tumor M2-PK measured by ELISA ranged between 0.82 and 27.10 U/mg protein in normal colon mucosa and between 1.96 and 242.40 U/mg protein in colon carcinoma. The tumor M2-PK content in the serum of 666 healthy blood donors was measured by ELISA and compared to sera from 15 colon carcinoma patients and showed a highly significant difference (Mann-Whitney rank sum test, p < 0.001). The values for the 50%-percentiles (median) of blood donors were 10.8 U/ml and 55.0 U/ml for colon carcinoma.
74 citations
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TL;DR: This study provides a mechanistic link between PKM2-induced metabolic remodeling and the antitumorigenic function of butyrate and demonstrates a widely applicable approach to uncovering unknown protein targets for small molecules with biological functions.
74 citations