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What Constitutes a Gluconeogenic Precursor?

Mark A Tetrick1, Jack Odle2

  • 1STATKING Clinical Services, Fairfield, OH, USA.

The Journal of Nutrition
|July 12, 2020
PubMed
Summary
This summary is machine-generated.

Even-chain length fatty acids (ECFAs) are not gluconeogenic precursors in fasting placental mammals via the tricarboxylic acid (TCA) cycle alone. However, they can be precursors in organisms with a glyoxylate cycle or via C3 metabolism of acetone.

Keywords:
acetoneanaplerotic reactionsfatty acidsgluconeogenesisgluconeogenic precursorsglyoxylate cycleprecursortricarboxylic acid cycle

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Area of Science:

  • Biochemistry
  • Metabolic Pathways
  • Mammalian Physiology

Background:

  • Gluconeogenic precursors are essential for net glucose synthesis in fasting mammals.
  • Known precursors include glycerol, lactate/pyruvate, amino acids, and odd-chain fatty acids, which are anaplerotic via the TCA cycle.
  • Even-chain length fatty acids (ECFAs) are typically not considered gluconeogenic precursors in placental mammals due to carbon loss via the TCA cycle.

Purpose of the Study:

  • To critically evaluate the definition and criteria for gluconeogenic precursors.
  • To investigate the gluconeogenic potential of ECFAs in fasting placental mammals.
  • To explore alternative metabolic pathways for ECFA conversion to glucose.

Main Methods:

  • Analysis of metabolic pathways, including the tricarboxylic acid (TCA) cycle and glyoxylate cycle.
  • Evaluation of anaplerotic contributions of various substrates to TCA cycle intermediates.
  • Consideration of C3 metabolism of acetone for ECFA conversion.

Main Results:

  • ECFAs do not contribute net carbon to glucose synthesis via the TCA cycle alone in fasting placental mammals.
  • ECFAs can serve as gluconeogenic precursors in organisms possessing a functional glyoxylate cycle.
  • Acetone metabolism (C3 pathway) offers a potential, albeit inefficient, route for ECFA gluconeogenesis in placental mammals.

Conclusions:

  • The classification of a substrate as a gluconeogenic precursor is context-dependent, requiring precise definition of the organism and physiological conditions.
  • ECFAs challenge the traditional definition of gluconeogenic precursors in placental mammals.
  • Further research is needed to fully elucidate the role of ECFAs in mammalian gluconeogenesis.