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Cellular respiration is a fundamental metabolic process that enables organisms to generate energy from organic molecules. One of its central pathways is the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, which plays a crucial role in energy production and biosynthetic processes.Conversion of Pyruvate to Acetyl-CoAThe pyruvate generated from glycolysis undergoes oxidative decarboxylation by the pyruvate dehydrogenase complex, producing acetyl-CoA, one molecule of NADH, and one...
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Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
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The cells of most organisms—including plants and animals—obtain usable energy through aerobic respiration, the oxygen-requiring version of cellular respiration. Aerobic respiration consists of four major stages: glycolysis, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation. The third major stage, the citric acid cycle, is also known as the Krebs cycle or tricarboxylic acid (TCA) cycle.
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La glucosa alimenta el ciclo TCA a través del lactato circulante

Sheng Hui1,2, Jonathan M Ghergurovich1,3, Raphael J Morscher1,2

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El lactato, no sólo la glucosa, es una fuente primaria de combustible para los tejidos y tumores de los mamíferos. Este estudio revela que el lactato

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Área de la Ciencia:

  • Las vías metabólicas
  • Utilización de los nutrientes
  • Metabolismo del cáncer

Sus antecedentes:

  • Los tejidos de los mamíferos utilizan nutrientes circulantes como la glucosa para obtener energía.
  • La glucosa suele metabolizarse completamente a través del ciclo del ácido tricarboxílico (TCA) en condiciones aeróbicas.
  • El lactato, un producto de la glucólisis anaeróbica, es una fuente potencial pero subestimada de nutrientes.

Objetivo del estudio:

  • Evaluar cuantitativamente el papel del lactato circulante como combustible metabólico en los tejidos de los mamíferos.
  • Investigar la contribución del lactato al ciclo del TCA en diversos tejidos y tumores.
  • Comprender la relación entre la glucólisis y el ciclo de TCA con respecto al lactato.

Principales métodos:

  • Examen sistemático de los flujos circulantes de metabolitos en ratones.
  • Infusión intravenosa de nutrientes marcados con 13C para rastrear las vías metabólicas.
  • Análisis cuantitativo del etiquetado intermedio del ciclo de TCA en tejidos y tumores.

Principales resultados:

  • El lactato presenta el mayor flujo de rotación circulatorio entre los metabolitos, superando a la glucosa tanto en ratones alimentados como en ratones en ayunas.
  • El 13C-lactato etiqueta ampliamente los intermediarios del ciclo TCA en todos los tejidos examinados.
  • En estados de ayuno, el lactato circulante es un importante contribuyente indirecto del carbono de glucosa al metabolismo de los tejidos TCA, excepto en el cerebro.
  • En los tumores de pulmón y páncreas, el lactato contribuye más a los intermediarios de TCA que la glucosa durante el ayuno.

Conclusiones:

  • El lactato es un sustrato circulante primario para el ciclo TCA en la mayoría de los tejidos y tumores de mamíferos.
  • La glicólisis y el ciclo de TCA no están acoplados, con el lactato actuando como un intermediario clave.
  • El papel del lactato como fuente de combustible es cuantitativamente significativo y justifica una mayor investigación, particularmente en el metabolismo del cáncer.