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Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathologica...

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Autores principales: Reiter, Russel J., Sharma, Ramaswamy, Rosales-Corral, Sergio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828708/
https://www.ncbi.nlm.nih.gov/pubmed/33466614
http://dx.doi.org/10.3390/ijms22020764
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author Reiter, Russel J.
Sharma, Ramaswamy
Rosales-Corral, Sergio
author_facet Reiter, Russel J.
Sharma, Ramaswamy
Rosales-Corral, Sergio
author_sort Reiter, Russel J.
collection PubMed
description Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.
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spelling pubmed-78287082021-01-25 Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases Reiter, Russel J. Sharma, Ramaswamy Rosales-Corral, Sergio Int J Mol Sci Review Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells. MDPI 2021-01-14 /pmc/articles/PMC7828708/ /pubmed/33466614 http://dx.doi.org/10.3390/ijms22020764 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Reiter, Russel J.
Sharma, Ramaswamy
Rosales-Corral, Sergio
Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title_full Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title_fullStr Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title_full_unstemmed Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title_short Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
title_sort anti-warburg effect of melatonin: a proposed mechanism to explain its inhibition of multiple diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828708/
https://www.ncbi.nlm.nih.gov/pubmed/33466614
http://dx.doi.org/10.3390/ijms22020764
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