Serine is a nonessential amino acid used in protein biosynthesis and can be derived from four possible sources: dietary intake, degradation of protein and phospholipids, biosynthesis from glycolysis intermediate 3-phosphoglycerate, or from glycine.
Serine is found in soybeans, nuts, eggs, lentils, shellfish, and meats. Serine is used to synthesize ethanolamine and choline for phospholipids. Serine is essential for the synthesis of sphingolipids and phosphatidylserine in CNS neurons. In the folate cycle, glycine and serine are interconverted. These methyltransferase reactions and interconversions are readily reversible depending on the needs of the folate cycle. Dietary serine is not fully converted to glycine; therefore, serine supplementation has little value, though is not harmful.
Glycine and serine’s interconversion are important in mitochondrial glycolysis. Glycolysis provides ATP and energy in most cell types. Serine-glycine biosynthesis is a component in glycolysis-diverting pathways and nucleotide biosynthesis. This is clinically important, and specifically evident, in cancer. Cancer cells use glycolysis to sustain anabolism for tumor growth. Genetic and functional evidence suggests that abnormalities in the glycine-serine pathway represent an essential process in cancer pathogenesis by promoting energy production and promoting defective purine synthesis.
Serine is also a cofactor for the transsulfuration enzyme cystathionine-β-synthase making its availability important for glutathione production.
References:
- Hart CE, Race V, Achouri Y, et al. Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. Am J Human Genet. 2007;80(5):931- 937.
- Hirabayashi Y, Furuya S. Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Prog Lipid Res. 2008;47(3):188-203.
- Kalhan SC, Hanson RW. Resurgence of serine: an often neglected but indispensable amino Acid. J Biol Chem. 2012;287(24):19786-19791.
- Kapalka GM. Nutr Herbal Ther Child Adol. Academic Press; 2010.
- Maddocks OD, Labuschagne CF, Adams PD, Vousden KH. Serine Metabolism Supports the Methionine Cycle and DNA/ RNA Methylation through De Novo ATP Synthesis in Cancer Cells. Molec Cell. 2016;61(2):210-221.
- Zeng JD, Wu WKK, Wang HY, Li XX. Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer. Pharmacol Res. 2019;149:104352.
- Dudman NP, Tyrrell PA, Wilcken DE. Homocysteinemia: depressed plasma serine levels. Metabo: Clin Exp. 1987;36(2):198-201.
- Milliner DS, Harris PC, Cogal AG, Lieske JC. Primary hyperoxaluria type 1. In: GeneReviews. University of Washington, Seattle; 2017.
- Ramos RJ, Pras-Raves ML, Gerrits J, et al. Vitamin B6 is essential for serine de novo biosynthesis. J Inherit Metab Dis. 2017;40(6):883-891.
- Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci. 2014;39(4):191-198.
- Gropper S SJ, Groff J. Adv Nutr Human Metab. 5th ed. Belmont, CA: Wadsworth, Cengage Learning; 2009.
- Jurgens P, Schwartau M, Doehn M. [Disorders of amino acid metabolism in a patient with identified thiamine deficiency]. Infusionstherapie klinische Ernahrung. 1982;9(6):312-316.
- Park YK, Linkswiler H. Effect of vitamin B6 depletion in adult man on the plasma concentration and the urinary excretion of free amino acids. JNutr. 1971;101(2):185-191.
Serine
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