Serine

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Not to be confused with Sarin.
For the French wine grape, see Serine (grape).
Serine
Skeletal formula Ball-and-stick model
Identifiers
CAS number 56-45-1 (L-isomer) YesY, 302-84-1 YesY, 312-84-5 (D-isomer) YesY
PubChem 617
ChemSpider 5736 (L-form) YesY, 597
UNII 452VLY9402 YesY
EC-number 206-130-6
DrugBank DB00133
ChEBI CHEBI:17115 YesY
ChEMBL CHEMBL11298 YesY
IUPHAR ligand 726
Jmol-3D images Image 1
Properties[2]
Molecular formula C3H7NO3
Molar mass 105.09 g mol−1
Appearance white crystals or powder
Density 1.603 g/cm3 (22 °C)
Melting point 246 °C decomp.
Solubility in water soluble
Acidity (pKa) 2.21 (carboxyl), 9.15 (amino)[1]
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Serine (abbreviated as Ser or S)[3] is an amino acid with the formula HO2CCH(NH2)CH2OH. It is one of the proteinogenic amino acids. Its codons in the genetic code are UCU, UCC, UCA, UCG, AGU and AGC. By virtue of the hydroxyl group, serine is classified as a polar amino acid.

Occurrence and biosynthesis[edit]

(S)-Serine (left) and (R)-serine (right) in zwitterionic form at neutral pH

This compound is one of the naturally occurring proteinogenic amino acids. Only the L-stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865. Its name is derived from the Latin for silk, sericum. Serine's structure was established in 1902.[4]

The biosynthesis of serine starts with the oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate and NADH. Reductive amination of this ketone followed by hydrolysis gives serine. Serine hydroxymethyltransferase catalyzes the reversible, simultaneous conversions of L-serine to glycine (retro-aldol cleavage) and 5,6,7,8-tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis).[5]

This compound may also be naturally produced when UV light illuminates simple ices such as a combination of water, methanol, hydrogen cyanide, and ammonia, suggesting that it may be easily produced in cold regions of space.[6]

Production[edit]

Industrially, L-serine is produced by fermentation, with an estimated 100-1000 tonnes per year produced.[7] In the laboratory, racemic serine can be prepared from methyl acrylate via several steps:[8]

Synthesis of dl-serine.png

Biological function[edit]

Metabolic[edit]

Cysteine synthesis from serine. Cystathionine beta synthase catalyzes the upper reaction and cystathionine gamma-lyase catalyzes the lower reaction.

Serine is important in metabolism in that it participates in the biosynthesis of purines and pyrimidines. It is the precursor to several amino acids including glycine and cysteine, and tryptophan in bacteria. It is also the precursor to numerous other metabolites, including sphingolipids and folate, which is the principal donor of one-carbon fragments in biosynthesis.

Structural role[edit]

Serine plays an important role in the catalytic function of many enzymes. It has been shown to occur in the active sites of chymotrypsin, trypsin, and many other enzymes. The so-called nerve gases and many substances used in insecticides have been shown to act by combining with a residue of serine in the active site of acetylcholine esterase, inhibiting the enzyme completely.

As a constituent (residue) of proteins, its side chain can undergo O-linked glycosylation, which may be functionally related to[clarification needed] diabetes.

It is one of three amino acid residues that are commonly phosphorylated by kinases during cell signaling in eukaryotes. Phosphorylated serine residues are often referred to as phosphoserine.

Serine proteases are a common type of protease.

Signaling[edit]

D-Serine, synthesized in the brain by serine racemase from L-serine (its enantiomer), serves as both a neurotransmitter and a gliotransmitter by coactivating NMDA receptors, making them able to open if they then also bind glutamate. D-serine is a potent agonist at the glycine site of the NMDA-type glutamate receptor. For the receptor to open, glutamate and either glycine or D-serine must bind to it. In fact, D-serine is a more potent agonist at the glycine site on the NMDAR than glycine itself. D-serine was only thought to exist in bacteria until relatively recently; it was the second D amino acid discovered to naturally exist in humans, present as a signalling molecule in the brain, soon after the discovery of D-aspartate. Had D amino acids been discovered in humans sooner, the glycine site on the NMDA receptor might instead be named the D-serine site.[9]

Gustatory sensation[edit]

Pure D-serine is an off-white crystalline powder with a very faint musty aroma. L-Serine is sweet with minor umami and sour tastes at high concentration. D-Serine is sweet with an additional minor sour taste at medium and high concentrations.[10]

Research for therapeutic use[edit]

D-Serine is being studied in rodents as a potential treatment for schizophrenia and L-serine is in FDA-approved human clinical trials as a possible treatment for ALS.[11] [12]

See also[edit]

References[edit]

  1. ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  2. ^ Weast, Robert C., ed. (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-512. ISBN 0-8493-0462-8. .
  3. ^ "Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Recommendations 1983)", Pure Appl. Chem. 56 (5), 1984: 595–624, doi:10.1351/pac198456050595 .
  4. ^ "Serine". The Columbia Encyclopedia 6th ed. encyclopedia.com. Retrieved 22 October 2012. 
  5. ^ Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000), Principles of Biochemistry (3rd ed.), New York: W. H. Freeman, ISBN 1-57259-153-6 .
  6. ^ Elsila, Jamie E.; Dworkin, Jason P.; Bernstein, Max P.; Martin, Mildred P.; Sandford, Scott A. (2007), "Mechanisms of Amino Acid Formation in Interstellar Ice Analogs", Astrophys. J. 660 (1): 911–18, Bibcode:2007ApJ...660..911E, doi:10.1086/513141 
  7. ^ Karlheinz Drauz, Ian Grayson, Axel Kleemann, Hans-Peter Krimmer, Wolfgang Leuchtenberger, Christoph Weckbecker (2005), "Amino Acids", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a02_057.pub2 
  8. ^ Carter, Herbert E.; West, Harold D. (1940), "dl-Serine", Org. Synth. 20: 81 ; Coll. Vol. 3: 774 .
  9. ^ Mothet, Jean-Pierre; Parent, Angèle T.; Wolosker, Herman; Brady, Roscoe O., Jr.; Linden, David J.; Ferris, Christopher D.; Rogawski, Michael A.; Snyder, Solomon H. (2000), "d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor", Proc. Natl. Acad. Sci. USA 97 (9): 4926–31, Bibcode:2000PNAS...97.4926M, doi:10.1073/pnas.97.9.4926, PMC 18334, PMID 10781100 .
  10. ^ http://www.springerlink.com/content/27074j4t2n508r7t/fulltext.html [Amino Acids. 2012 May 16. [Epub ahead of print] Gustatory sensation of L: - and D: -amino acids in humans. Kawai M, Sekine-Hayakawa Y, Okiyama A, Ninomiya Y.
  11. ^ Balu, DT; Li, Y; Puhl, MD; Benneyworth, MA; Basu, AC; Takagi, S; Bolshakov, VY; Coyle, JT (2013), "Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction", Proc Natl Acad Sci USA 110 (26): E2400–9, doi:10.1073/pnas.1304308110, PMID 23729812 
  12. ^ Dunlop, R, "The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation", PLOS One, doi:10.1371/journal.pone.0075376 

External links[edit]