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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7828708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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