Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria
Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy, Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy
Abstract
Background: Deficiencies of the monoamine neurotransmitters, such as dopamine synthesized from Tyr and serotonin synthesized from Trp, are of concern in PKU. Our objective was to utilize metabolomics analysis to assess monoamine metabolites in subjects with PKU consuming amino acid medical foods (AA-MF) and glycomacropeptide medical foods (GMP-MF).
Methods: Subjects with PKU consumed a low-Phe diet combined with AA-MF or GMP-MF for 3weeks each in a randomized, controlled, crossover study. Metabolomic analysis was conducted by Metabolon, Inc. on plasma (n=18) and urine (n=9) samples. Catecholamines and 6-sulfatoxymelatonin were measured in 24-h urine samples.
Results: Intake of Tyr and Trp was ~50% higher with AA-MF, and AA-MF were consumed in larger quantities, less frequently during the day compared with GMP-MF. Performance on neuropsychological tests and concentrations of neurotransmitters derived from Tyr and Trp were not significantly different with AA-MF or GMP-MF. Plasma serotonin levels of gut origin were higher in subjects with variant compared with classical PKU, and with GMP-MF compared with AA-MF in subjects with variant PKU. Metabolomics analysis identified higher levels of microbiome-derived compounds synthesized from Tyr, such as phenol sulfate, and higher levels of compounds synthesized from Trp in the kynurenine pathway, such as quinolinic acid, with ingestion of AA-MF compared with GMP-MF.
Conclusions: The Tyr from AA-MF is less bioavailable due, in part, to greater degradation by intestinal microbes compared with the Tyr from prebiotic GMP-MF. Research is needed to understand how metabolism of Trp via the kynurenine pathway and changes in the intestinal microbiota affect health for individuals with PKU. This trial is registered at www.clinicaltrials.gov as NCT01428258.
Keywords: 6-sulfatoxymelatonin; Catecholamines; Glycomacropeptide; Intestinal microbiota; Phenol sulfate; Serotonin.
Conflict of interest statement
Conflict of Interest: DMN is a co-inventor on U.S. Patent 8,604,168 B2, “Glycomacropeptide Medical Foods for Nutritional Management of Phenylketonuria and other Metabolic Disorders,” which is held by the Wisconsin Alumni Research Foundation and licensed to Cambrooke Therapeutics, LLC. DMN is a consultant to Arla Foods Ingredients. BMS, MKC, SGM, GMR, FR, and HLL have no conflicts of interest to declare. FR has received consulting fees from Cambrooke Therapeutics. The remaining authors declare no conflict of interest related to this research.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Source: PubMed