The effects of a low protein diet on amino acids and enzymes in the serine synthesis pathway in mice.
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.
Antflick
Jordan E
JE
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, ON, M5S 3M2, Canada.
Baker
Glen B
GB
Hampson
David Richard
DR
D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001835:Body Weight; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D012695:L-Serine Dehydratase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000378:metabolism*; D012694:Serine / Q000096:biosynthesis* / Q000378:metabolism; D000099300:Serine Racemase
D000596:Amino Acids; D004044:Dietary Proteins; D012695:L-Serine Dehydratase; D010744:Phosphoric Monoester Hydrolases; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C022394:phosphoserine phosphatase