The effects of a low protein diet on amino acids and enzymes in the serine synthesis pathway in mice

Amino Acids
Jordan E AntflickDavid R Hampson

Abstract

L-serine is required for cellular and tissue growth and is particularly important in the immature brain where it acts as a crucial neurotrophic factor. In this study, the levels of amino acids and enzymes in the L-serine biosynthetic pathway were examined in the forebrain, cerebellum, liver, and kidney after the exposure of mice to protein-restricted diets. The levels of L-serine, D-serine, and L-serine-O-phosphate were quantified by HPLC and quantitative Western blotting was used to measure changes in protein levels of five enzymes in the pathway. The L-serine biosynthetic enzyme phosphoserine phosphatase was strongly upregulated, while the serine degradative enzymes serine racemase and serine dehydratase were downregulated in the livers and kidneys of mice fed low (6%) or very low (2%) protein diets for 2 weeks compared with mice fed a normal diet (18% protein). No changes in these enzymes were seen in the brain. The levels of L-serine increased in the livers of mice fed 2% protein; in contrast, D-serine levels were reduced below the limit of detection in the livers of mice given either the 6 or 2% diets. D-Serine is a co-agonist at the NMDA class of glutamate receptors; no alterations in NMDA-R1 subunit expression were obser...Continue Reading

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Citations

May 9, 2012·The Journal of Biological Chemistry·Satish C Kalhan, Richard W Hanson
Mar 8, 2013·Science Translational Medicine·Anders H BergS Ananth Karumanchi
Jun 3, 2014·Orphanet Journal of Rare Diseases·Kara R VogelK Michael Gibson
Aug 3, 2012·Expert Review of Neurotherapeutics·Emerson A NunesSerdar M Dursun
Dec 8, 2011·Journal of Neurochemistry·Jordan E Antflick, David R Hampson
Feb 8, 2011·Neuropharmacology·Viviane LabrieJohn C Roder

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