What intermediate is formed in the metabolism of aromatic amino acids that enters the gluconeogenic pathway?

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From the Research

The intermediate formed during the metabolism of aromatic amino acids (phenylalanine and tyrosine) that enters the gluconeogenic pathway is fumarate. When these aromatic amino acids are catabolized, they are first converted to various intermediates through a series of enzymatic reactions. Phenylalanine is first hydroxylated to form tyrosine, which is then further metabolized. The pathway continues through homogentisate, maleylacetoacetate, and fumarylacetoacetate. The fumarylacetoacetate is then cleaved to form fumarate and acetoacetate. Fumarate is a direct intermediate of the tricarboxylic acid (TCA) cycle and can enter gluconeogenesis through conversion to malate, then oxaloacetate, which is a key gluconeogenic precursor. This makes phenylalanine and tyrosine partially gluconeogenic amino acids, as the fumarate portion can contribute to glucose synthesis while the acetoacetate portion is ketogenic. Tryptophan, another aromatic amino acid, can also produce small amounts of alanine and pyruvate that can enter gluconeogenesis, though its metabolism is more complex and primarily leads to other metabolites 1.

Some key points to consider in the metabolism of aromatic amino acids include:

  • The role of tyrosine aminotransferase in the transamination of tyrosine and other aromatic amino acids 2
  • The importance of the TCA cycle in the metabolism of amino acids, including the conversion of fumarate to malate and oxaloacetate 3
  • The complex metabolism of tryptophan, which can lead to the production of various metabolites, including alanine and pyruvate 1
  • The potential for the accumulation of toxic metabolites, such as fumarylacetoacetate and maleylacetoacetate, in the absence of certain enzymes, such as fumarylacetoacetate hydrolase 4

Overall, the metabolism of aromatic amino acids is complex and involves the conversion of these amino acids into various intermediates that can enter the TCA cycle and gluconeogenesis. The most recent and highest quality study on this topic is from 2018, which provides a comprehensive review of the metabolism of aromatic amino acids and their role in the health of plants and animals 1.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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