Serine

    Serine is a nonessential amino acid used in protein biosynthesis and can be derived from four possible sources: dietary intake, degradation of proteins and phospholipids, biosynthesis of the 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 is of little value, although not harmful.

    Interconversion of glycine and serine is important in mitochondrial glycolysis. Glycolysis provides ATP and energy in most cell types. Serine-glycine biosynthesis is a component in the glycolysis bypass pathways and nucleotide biosynthesis. This is clinically important and is particularly 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 the pathogenesis of cancer, 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.

    High dietary intake of serine-rich foods, or supplementation, may result in elevated levels.

    Due to the cofactors required for serine metabolism, deficiencies of these nutrients can result in elevated serine levels. Administration of nutrients such as vitamin B₆ or B₁ has been shown to reduce serine levels, as well as other amino acids.

  Given its association with the folate cycle, plasma serine levels may be low or high with homocysteinemia and methylation defects; support with vitamin B₆, B₁₂, folate, or betaine may result in normalized homocysteine, as well as serine.

    Low serine may be due to decreased intake, or GI malabsorption and maldigestion.

 A serine biosynthetic pathway requires the vitamin B₆-dependent enzyme phosphoserine aminotransferase. Thus, a functional requirement for vitamin B₆ may contribute to low serine levels.

    Given its association with the folate cycle, plasma serine levels may be low or high with homocysteinemia and methylation defects; support with vitamin B₆, B₁₂, folate, or betaine may result in normalized homocysteine ​​as well as serine