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Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI)
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland; Department of Clinical Genetics, Turku University Hospital, Turku, Finland.
Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
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2016 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 9, 1361-1375 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Lysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria with defective transport of cationic amino acids in epithelial cells in the small intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is characterized by protein malnutrition, failure to thrive and hyperammonemia. Many patients also suffer from combined hyperlipidemia and chronic kidney disease (CKD) with an unknown etiology.

METHODS: Here, we studied the plasma metabolomes of the Finnish LPI patients (n=26) and healthy control individuals (n=19) using a targeted platform for analysis of amino acids as well as two analytical platforms with comprehensive coverage of molecular lipids and polar metabolites.

RESULTS: Our results demonstrated that LPI patients have a dichotomy of amino acid profiles, with both decreased essential and increased non-essential amino acids. Altered levels of metabolites participating in pathways such as sugar, energy, amino acid and lipid metabolism were observed. Furthermore, of these metabolites, myo-inositol, threonic acid, 2,5-furandicarboxylic acid, galactaric acid, 4-hydroxyphenylacetic acid, indole-3-acetic acid and beta-aminoisobutyric acid associated significantly (P<0.001) with the CKD status. Lipid analysis showed reduced levels of phosphatidylcholines and elevated levels of triacylglycerols, of which long-chain triacylglycerols associated (P<0.01) with CKD.

CONCLUSIONS: This study revealed an amino acid imbalance affecting the basic cellular metabolism, disturbances in plasma lipid composition suggesting hepatic steatosis and fibrosis and novel metabolites correlating with CKD in LPI. In addition, the CKD-associated metabolite profile along with increased nitrite plasma levels suggests that LPI may be characterized by increased oxidative stress and apoptosis, altered microbial metabolism in the intestine and uremic toxicity.

Place, publisher, year, edition, pages
Saunders Elsevier, 2016. Vol. 65, no 9, 1361-1375 p.
Keyword [en]
Lysinuric protein intolerance; Chronic kidney disease; Combined hyperlipidemia; Metabolomics; Lipidomics
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-59379DOI: 10.1016/j.metabol.2016.05.012ISI: 000381449600015PubMedID: 27506743Scopus ID: 2-s2.0-84975105763OAI: oai:DiVA.org:oru-59379DiVA: diva2:1136166
Note

Funding Agencies:

Turku University Foundation  

Finnish Cultural Foundation  

Finnish Concordia Fund  

Maud Kuistila Memorial Foundation  

Paivikki and Sakari Sohlberg Foundation  

Foundation for Pediatric Research  

Tyks Foundation  

Magnus Ehrnrooth Foundation  

Turku University Hospital ERVA Fund 

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2017-09-08Bibliographically approved

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CiteExportLink to record
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