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Related Concept Videos

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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The Citric Acid Cycle: Output01:28

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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
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The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
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Overview of Fatty Acid Metabolism01:28

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Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
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Pyruvate Oxidation01:15

Pyruvate Oxidation

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After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
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The Citric Acid Cycle: Overview01:37

The Citric Acid Cycle: Overview

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In aerobic organisms, the citric acid cycle is the second stage of cellular respiration wherein molecules derived from the breakdown of carbohydrates, proteins, and fats are oxidized into carbon dioxide and energy. This process is also known as the tricarboxylic acid (TCA) cycle as the first product of the cycle, citric acid, contains three carboxyl groups in its structure. Alternatively, this cycle is also referred to as the Krebs cycle, in honor of its discoverer Sir Hans Krebs.
The citric...
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Updated: Jun 12, 2025

Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
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Metabolic Pathway Tracing for NAD+ Synthesis and Consumption.

Tumpa Dutta1, Stephen J Gardell2

  • 1Translational Research Institute, AdventHealth, Orlando, FL, USA. tumpa.dutta@adventhealth.com.

Methods in Molecular Biology (Clifton, N.J.)
|June 11, 2025
PubMed
Summary
This summary is machine-generated.

Nicotinamide adenine dinucleotide (NAD+) is crucial for metabolism and health. Metabolic pathway tracing reveals how NAD+ synthesis and consumption impact levels, offering insights into aging and disease.

Keywords:
Mass isotopomer distribution profilingMass spectrometryNAD+ consumptionNAD+ fluxNAD+ metabolismNAD+ synthesisStable isotope tracing

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Area of Science:

  • Biochemistry
  • Metabolomics
  • Aging Research

Background:

  • Nicotinamide adenine dinucleotide (NAD+) is a vital cellular metabolite involved in metabolism, redox reactions, and cellular signaling.
  • Declining NAD+ levels are associated with aging and chronic diseases, but the underlying causes (synthesis vs. consumption) are unclear.
  • Static NAD+ measurements are insufficient to understand the dynamic metabolic pathways governing its levels.

Purpose of the Study:

  • To investigate the dynamic processes of NAD+ synthesis and consumption.
  • To elucidate the contributions of different pathways to steady-state NAD+ concentrations.
  • To critically evaluate the role of NAD+ metabolism in aging and disease.

Main Methods:

  • Metabolic pathway tracing using stable isotope-labeled NAD+ precursors (e.g., nicotinamide, nicotinic acid, tryptophan).
  • High-resolution mass spectrometry (HRMS) to track precursor fate and metabolic products (NADH, NADP, NADPH).
  • Analysis of NAD+ synthesis and degradation pathways in various biological samples (cells, tissues, biofluids).

Main Results:

  • Metabolic pathway tracing successfully differentiated NAD+ synthesis and consumption rates.
  • The technique identified the metabolic fate of NAD+ precursors and downstream products.
  • This approach is applicable across diverse biological systems from cell cultures to clinical samples.

Conclusions:

  • Metabolic pathway tracing is a versatile tool for understanding NAD+ homeostasis.
  • It provides critical insights into the dynamic regulation of NAD+ metabolism.
  • This technique can help clarify the link between NAD+ levels, aging, and chronic diseases.