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Related Concept Videos

The Citric Acid Cycle: Output01:28

The Citric Acid Cycle: Output

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The citric acid cycle is termed an amphibolic pathway as it operates both anabolically and catabolically. The cyclic reactions balance the flux of the substrates to provide an optimal concentration of NADH and ATP to the cell.
Regulation of Citric Acid Cycle
The citric acid cycle is regulated in several ways, including feedback inhibition, regulation of enzyme activities, and associated anaplerotic or cataplerotic pathways.
The primary substrate of the TCA cycle—acetyl CoA—is...
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Respiration Pathways01:26

Respiration Pathways

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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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The Citric Acid Cycle02:36

The Citric Acid Cycle

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The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three NADH molecules, one FADH2 molecule, and two CO2 molecules.
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Fates of Pyruvate01:20

Fates of Pyruvate

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Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
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Overview of Carbohydrate Metabolism01:19

Overview of Carbohydrate Metabolism

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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.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
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Products of the Citric Acid Cycle00:53

Products of the Citric Acid Cycle

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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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Liquid Chromatography Coupled to Refractive Index or Mass Spectrometric Detection for Metabolite Profiling in Lysate-based Cell-free Systems
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Glucose feeds the TCA cycle via circulating lactate.

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

  • 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.

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Lactate, not just glucose, is a primary fuel source for mammalian tissues and tumors. This study reveals lactate

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Area of Science:

  • Metabolic pathways
  • Nutrient utilization
  • Cancer metabolism

Background:

  • Mammalian tissues utilize circulating nutrients like glucose for energy.
  • Glucose is typically fully metabolized via the tricarboxylic acid (TCA) cycle under aerobic conditions.
  • Lactate, a product of anaerobic glycolysis, is a potential but underappreciated nutrient source.

Purpose of the Study:

  • To quantitatively assess the role of circulating lactate as a metabolic fuel in mammalian tissues.
  • To investigate the contribution of lactate to the TCA cycle in various tissues and tumors.
  • To understand the relationship between glycolysis and the TCA cycle concerning lactate.

Main Methods:

  • Systematic examination of circulating metabolite fluxes in mice.
  • Intravenous infusion of 13C-labeled nutrients to trace metabolic pathways.
  • Quantitative analysis of TCA cycle intermediate labeling in tissues and tumors.

Main Results:

  • Lactate exhibits the highest circulatory turnover flux among metabolites, exceeding glucose in both fed and fasted mice.
  • 13C-lactate extensively labels TCA cycle intermediates across all examined tissues.
  • In fasted states, circulating lactate is a major indirect contributor of glucose carbon to tissue TCA metabolism, except in the brain.
  • In lung and pancreatic tumors, lactate contributes more to TCA intermediates than glucose during fasting.

Conclusions:

  • Lactate is a primary circulating substrate for the TCA cycle in most mammalian tissues and tumors.
  • Glycolysis and the TCA cycle are uncoupled, with lactate acting as a key intermediary.
  • Lactate's role as a fuel source is quantitatively significant and warrants further investigation, particularly in cancer metabolism.