Compendium of the most significant studies with reference to properties, intake, effects.

Barrasa MI, Harel NY, Alwine JC. The phosphorylation status of the serine-rich region of the human cytomegalovirus 86-kilodalton major immediate-early protein IE2/IEP86 affects temporal viral gene expression. J Virol. 2005 Feb;79(3):1428-37. doi: 10.1128/JVI.79.3.1428-1437.2005. 

Abstract. The 86-kDa major immediate-early protein (IE2/IEP86) of human cytomegalovirus (HCMV) contains a serine-rich region (amino acids 258 to 275) with several consensus casein kinase II (CKII) sites. We performed extensive mutational analysis of this region, changing serines to alternating alanines and glycines. Mutation of the serines between amino acids 266 and 275 eliminated in vitro phosphorylation by CKII. In vitro CKII phosphorylation of the serines between amino acids 266 and 269 or between amino acids 271 and 275 inhibited the ability of IE2/IEP86 to bind to TATA-binding protein.

Menou A, Duitman J, Flajolet P, Sallenave JM, Mailleux AA, Crestani B. Human airway trypsin-like protease, a serine protease involved in respiratory diseases. Am J Physiol Lung Cell Mol Physiol. 2017 May 1;312(5):L657-L668. doi: 10.1152/ajplung.00509.2016.

Abstract. More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. 

Pariser H, Herradon G, Ezquerra L, Perez-Pinera P, Deuel TF. Pleiotrophin regulates serine phosphorylation and the cellular distribution of beta-adducin through activation of protein kinase C. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12407-12. doi: 10.1073/pnas.0505901102. 

Abstract. Pleiotrophin (PTN) was found to regulate tyrosine phosphorylation of beta-adducin through the PTN/receptor protein tyrosine phosphatase (RPTP)beta/zeta signaling pathway. We now demonstrate that PTN stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (PK) C substrate domain of beta-adducin through activation of either PKC alpha or beta. We also demonstrate that PTN stimulates translocation of phosphoserine 713 and 726 beta-adducin either to nuclei, where it associates with nuclear chromatin and with centrioles of dividing cells, or to a membrane-associated site, depending on the phase of cell growth. 

Le Douce J, Maugard M, Veran J, Matos M, Jégo P, Vigneron PA, Faivre E, Toussay X, Vandenberghe M, Balbastre Y, Piquet J, Guiot E, Tran NT, Taverna M, Marinesco S, Koyanagi A, Furuya S, Gaudin-Guérif M, Goutal S, Ghettas A, Pruvost A, Bemelmans AP, Gaillard MC, Cambon K, Stimmer L, Sazdovitch V, Duyckaerts C, Knott G, Hérard AS, Delzescaux T, Hantraye P, Brouillet E, Cauli B, Oliet SHR, Panatier A, Bonvento G. Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer's Disease. Cell Metab. 2020 Mar 3;31(3):503-517.e8. doi: 10.1016/j.cmet.2020.02.004.

Abstract. Here, we show that the astrocytic l-serine biosynthesis pathway, which branches from glycolysis, is impaired in young  Alzheimer's disease (AD) mice and in AD patients. l-serine is the precursor of d-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity.

Baumgart F, Rodríguez-Crespo I. D-amino acids in the brain: the biochemistry of brain serine racemase. FEBS J. 2008 Jul;275(14):3538-45. doi: 10.1111/j.1742-4658.2008.06517.x. 

Abstract. It has been recently established that in various brain regions D-serine, the product of serine racemase, occupies the so-called 'glycine site' within N-methyl D-aspartate receptors. Mammalian brain serine racemase is a pyridoxal-5' phosphate-containing enzyme that catalyzes the racemization of L-serine to D-serine. It has also been shown to catalyze the alpha,beta-elimination of water from L-serine or D-serine to form pyruvate and ammonia. 

Yang JH, Wada A, Yoshida K, Miyoshi Y, Sayano T, Esaki K, Kinoshita MO, Tomonaga S, Azuma N, Watanabe M, Hamase K, Zaitsu K, Machida T, Messing A, Itohara S, Hirabayashi Y, Furuya S. Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain. J Biol Chem. 2010 Dec 31;285(53):41380-90. doi: 10.1074/jbc.M110.187443.

Abstract. The present study provides definitive proof that L-serine-synthesized endogenously via the phosphorylated pathway is a key rate-limiting factor for maintaining steady-state levels of D-serine in adult brain. Furthermore, NMDA-evoked transcription of Arc, an immediate early gene, was diminished in the hippocampus of conditional knock-out mice. Thus, this study demonstrates that in mature neuronal circuits L-serine availability determines the rate of D-serine synthesis in the forebrain and controls NMDA receptor function at least in the hippocampus.

Ai X, Yan J, Pogwizd SM. Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders. Cell Signal. 2021 Oct;86:110070. doi: 10.1016/j.cellsig.2021.110070.

Abstract.  The focus of this review is to introduce serine-threonine protein phosphatase regulation of Cx43 phosphorylation state and cell-to-cell communication, and its impact on arrhythmogenesis in the setting of chronic heart failure and myocardial ischemia, as well as on atrial fibrillation. We also discuss the therapeutic potential of modulating protein phosphatases to treat arrhythmias in these clinical settings.

Morioka M, Kawano T, Yano S, Kai Y, Tsuiki H, Yoshinaga Y, Matsumoto J, Maeda T, Hamada J, Yamamoto H, Fukunaga K, Kuratsu J. Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia. Biochem Biophys Res Commun. 2006 Aug 18;347(1):273-8. doi: 10.1016/j.bbrc.2006.06.096.

Abstract. We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation.

Serine is a non-essential polar amino acid present in the human body and important in many proteins. It is synthesised by the body and is involved in the metabolism of fats and fatty acids and in muscle growth while maintaining a healthy immune system.

 is the α-hydroxymethyl-substituted amino acid of proteins. Amino acids play a key metabolic function in the human body and are constituents of proteins. 

As food additives they perform different functions: preservatives, flavour enhancers, food supplements and more.

Amino acids together with their salts are used in cosmetics as conditioning agents for both hair and skin (e.g. as moisturisers and other similar functions). Moisturisers are different in nature: the best are the natural ones that exploit the mechanism of integration between the ingredient and the skin by moisturising the horny hydrolipid film, i.e. the thin protective layer that covers the epidermis protecting it from harmful external microbes, keeping the skin moisturised and supple and its pH or acidity value between 4 and 6.  Then there are the occlusive moisturisers, usually derived from petroleum (Paraffinum, Paraffinum liquidum and others), but also triglycerides, lanolin oil, natural or synthetic waxes, fatty acid esters and others that create an artificial occlusive layer on the stratum corneum of the skin with the advantage of accelerating the protective process but with the disadvantage of preventing the skin's natural transpiration.

α-amino acids that have similar physical structures undergo similar changes with regard to solubility in water/ethanol mixtures, and technologies to separate α-amino acids from industrial residues, which may not even be innocuous, are constantly being improved. However, many data on the solubility in water-ethanol and ethanol of some α-amino acids are contradictory or even lacking, and the effects of ethanol on the solubility of amino acids may be different. Overall, the scientific literature considers that α-amino acids do not pose significant problems for human health when taken orally, except in people with certain genetic diseases.

Food safety: amino acid α generally considered safe.

Cosmetic safety: amino acid α generally considered safe when formulated to be non-irritant.

In commercial products, especially cosmetics, it is usually used to replace Serine, L-Serine. It is a proteinogenic, aliphatically neutral amino acid essential for the synthesis of phosphatidylserine, the membrane of brain cells.  It has the function of maintaining a healthy immune system through the production of antibodies and immune haemoglobin.

It occurs as a white crystalline powder, sweetish taste, soluble in water and acid, insoluble in alcohol and ether. 

What it is used for and where

Medical

Serine is used as a dietary supplement to help improve memory function.

L-serine is an essential amino acid for the survival of neurons and is essential for brain development (1) and can be taken up from food, from glycine, via the phosphorylated pathway 

D-serine is found in the adult brain and particularly present in forebrain regions where it acts as a glycine co-agonist of NMDA receptors.

Cosmetics

Nourishing agent, assisting in the production of new skin cells with a moisturising function. Can be made into liposomes with phospholipids and mixed with other active ingredients for a better moisturising effect.

Serine studies

Typical commercial product characteristics L-serine

• Molecular Formula   C₃H₇NO₃
• Linear Formula  HOCH₂CH(NH₂)CO₂H
• Molecular Weight    105.09
• Exact Mass   105.042595
• CAS  56-45-1    25821-52-7
• UNII    452VLY9402
• EC Number   200-274-3
• DSSTox Substance ID  
• IUPAC  (2S)-2-amino-3-hydroxypropanoic acid
• InChI=1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1 
• InChl Key      MTCFGRXMJLQNBG-REOHCLBHSA-N
• SMILES   C(C(C(=O)O)N)O
• MDL number  MFCD00064224
• PubChem Substance ID    24899605
• ChEBI  17115
• RXCUI    9671    
• Beilstein    1721404
• NSC   760115
• RTECS   VT8100000
• eCl@ss      32160406
• NCI   C29613

Synonyms

• beta-Hydroxyalanine
• (S)-2-Amino-3-hydroxypropionic acid

References______________________________________________________________________

(1) Hirabayashi Y, Furuya S. Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Prog Lipid Res. 2008 May;47(3):188-203. doi: 10.1016/j.plipres.2008.01.003. 

(2) Snell K. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul. 1984;22:325-400. doi: 10.1016/0065-2571(84)90021-9.