Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria

Douglas, Teresa D.; Nucci, Anita; Berry, Ann M; Henes, Sarah T.; Singh, Rani H.

doi:10.1002/jmd2.12076

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Whole blood samples were collected from the shunt at 2, 5, 10, 20, 30, 40 and 60 min post-injection into heparinised Eppendorf tubes and placed immediately on ice. Aliquots of whole blood and plasma were counted using a γ-counter, and additional plasma aliquots were stored at -80 °C (full details in Supplementary materials) until sent to Alta Bioscience Ltd (Redditch, UK, https://altabioscience.com ) for analysis of the large neutral amino acids (LNAA) (histidine, methionine, leucine, isoleucine, valine, phenylalanine, tyrosine and tryptophan), concentration in nmol/ml [ 25 ]. The plasma/whole blood and free/protein-incorporated [ 11 C]leucine ratios were measured by γ-counting (full details in Supplementary materials).…”

Section: Methodsmentioning

confidence: 99%

Measurement of Protein Synthesis Rate in Rat by [11C]Leucine PET Imaging: Application to the TgF344-AD Model of Alzheimer’s Disease

et al. 2022

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Long-term memory requires stable protein synthesis and is altered in Alzheimer’s disease (AD). This study aimed to implement a method to measure the cerebral protein synthesis rate (PSR) with [11C]leucine PET in vivo in rats and evaluate potential PSR alterations longitudinally (6, 12 and 18 months old) in the TgF344-AD rat model of AD. Wistar, wild-type (WT) and TgF344-AD rats (TG) were scanned for 60 min with [11C]leucine. Arterial blood activity was monitored online and with discrete whole blood and plasma samples by γ-counting in Wistar rats, WT (n = 4) and TG (n = 5). Unlabelled amino acids were measured in plasma. The sensitivity of [11C]leucine PET to measure alterations in PSR was assessed in Wistar rats by injection of PSR inhibitor anisomycin before PET acquisition. Anisomycin administration significantly reduced the net uptake rate constant (Kcplx) of [11C]leucine and PSR, proving the suitability of the method. For the longitudinal study, averaged population-based input functions were used to calculate PSR. We found a significant genotype effect on PSR (decrease in TG vs WT) only in the globus pallidus. This study suggests that [11C]leucine PET is sensitive enough to measure brain PSR in rat but that cross-sectional design with individual input function should be preferred.

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Section: Methodsmentioning

confidence: 99%

Measurement of Protein Synthesis Rate in Rat by [11C]Leucine PET Imaging: Application to the TgF344-AD Model of Alzheimer’s Disease

et al. 2022

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“…According to conclusion of study the P: T (Phe: Tyr) ratio is significantly dependent on dietary LNAA and plasma LNAA concentrations. In addition, in patients with PKU, the P: T ratio and valine may be effective clinical indicators in determining the metabolic balance of LNAA and the quality of diet LNAA (Hoeksma et al, 2009;Douglas et al, 2019).…”

Section: Artificial Sweetenersmentioning

confidence: 99%

The Current Information in Nutrition Therapy of Phenylketonuria

Köseoğlu

Çelikel

2020

European Journal of Science and Technology

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Phenylketonuria (PKU) is one of the most common congenital metabolism disorders. In this disease, due to the defect in the phenylalanine hydroxylase enzyme made in the liver, phenylalanine cannot follow the tyrosine pathway and the symptoms of phenylalanine metabolites occur in body tissues, organs and body fluids. Nutritional therapy is applied in the treatment of the disease depending on the type of PKU. The purpose of nutritional therapy is to minimize the amount of phenylalane taken with nutrients and to keep the level of blood phenylale within normal limits. For this reason, a special nutrition program is applied throughout the life from the newborn period. The first step in the diagnosis of PKU is to determine the level of plasma phenylalanine with the blood sample taken from the heel of the newborn. Different types of hyperphenylalaninemias are seen as a result of phenylalanine hydroxylase enzyme and tetrahydrobiopterine (BH4) metabolism disorder. In the formation of BH4 cofactor defects, there is a defect in the metabolism of tetrahydrobiopterin, and its findings are different from classical PKU. In addition to the proper nutrition program, large neutral aminoacids (LNAA) and sapropterin (a synthetic form of BH4) are used in the treatment, according to the results of new studies. In classical PKU, when there is no medical nutrition treatment specific to the disease, many clinical findings such as mental retardation, skin-hair pigmentation disorders, growth retardation, microcephaly, epilepsy, behavioral disorders, hyperactivity and anxiety can be seen. In order for the symptoms associated with PKU to decrease and individuals with PKU to live a healthier life, they should comply with dietary treatment that includes protein-restricted, high-fat and carbohydrate-containing foods except for vegetables and fruits limited from phenylalanine Essential protein sources should be provided with special formulas with added tyrosine and essential amino acids and foods enriched with vitamins and minerals that may be deficient. However, the implementation of an effective nutrition therapy is possible by providing communication between the healthcare team and the family and introducing the disease to the family, and training in the development and treatment of the disease.

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Current Advances and Material Innovations in the Search for Novel Treatments of Phenylketonuria

Delbreil,

Dhondt,

Kenaan El Rahbani

et al. 2024

Adv Healthcare Materials

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Phenylketonuria (PKU) is a genetically inherited disease caused by a mutation of the gene encoding phenylalanine hydroxylase (PAH) and is the most common inborn error of amino acid metabolism. A deficiency of PAH leads to increased blood and brain levels of phenylalanine (Phe), which may cause permanent neurocognitive symptoms and developmental delays if untreated. Current management strategies for PKU consist of early detection through neonatal screening and implementation of a restrictive diet with minimal amounts of natural protein in combination with Phe‐free supplements and low‐protein foods to meet nutritional requirements. For milder forms of PKU, oral treatment with synthetic sapropterin (BH4), the cofactor of PAH, may improve metabolic control of Phe and allow for more natural protein to be included in the patient's diet. For more severe forms, daily injections of pegvaliase, a PEGylated variant of phenylalanine ammonia‐lyase (PAL), may allow for normalization of blood Phe levels. However, the latter treatment has considerable drawbacks, notably a strong immunogenicity of the exogenous enzyme and the attached polymeric chains. Research for novel therapies of PKU has made use of innovative materials for drug delivery and state‐of‐the‐art protein engineering techniques to develop treatments which are safer, more effective, and potentially permanent.This article is protected by copyright. All rights reserved

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Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria

Cited by 4 publications

References 34 publications

Measurement of Protein Synthesis Rate in Rat by [11C]Leucine PET Imaging: Application to the TgF344-AD Model of Alzheimer’s Disease

Measurement of Protein Synthesis Rate in Rat by [11C]Leucine PET Imaging: Application to the TgF344-AD Model of Alzheimer’s Disease

The Current Information in Nutrition Therapy of Phenylketonuria

Current Advances and Material Innovations in the Search for Novel Treatments of Phenylketonuria

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