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

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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 observed in liver or brain after protein restriction. These findings demonstrate that the expression of l-serine synthetic and degradative enzymes display reciprocal changes in the liver and kidney to increase l-serine and decrease d-serine levels under conditions of protein restriction, and that the brain is insulated from such changes.

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Acknowledgments

We thank Dr. Patrick Stover for the antibody to SHMT. This research was funded through an operating grant to DRH and GBB from the Canadian Institutes for Health Research (#MOP81179), and a graduate student scholarship to JEA from the Natural Sciences and Engineering Research Council of Canada. The expert technical assistance of Ms. Gail Rauw is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, ON, M5S 3M2, Canada

    Jordan E. Antflick & David Richard Hampson

  2. Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, T6G 2G3, Canada

    Glen B. Baker

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  1. Jordan E. Antflick
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  2. Glen B. Baker
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Correspondence to David Richard Hampson.

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726_2009_387_MOESM1_ESM.tif

Expression of the NMDA-R1 receptor subunit in mice fed the 18% or 2% protein diets. No significant changes were detected in NMDA-R1 expression in forebrain, liver, or kidney tissue. In both the liver and kidney, a high degree of variability in NMDA-R1 expression was observed in individual mice irrespective of the diet consumed. Values represent means ± SEM from 4 mice for each group. (TIFF 30789 kb)

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Antflick, J.E., Baker, G.B. & Hampson, D.R. The effects of a low protein diet on amino acids and enzymes in the serine synthesis pathway in mice. Amino Acids 39, 145–153 (2010). https://doi.org/10.1007/s00726-009-0387-8

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  • DOI: https://doi.org/10.1007/s00726-009-0387-8

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