Serine
IUPAC name Serine
Other names 2-Amino-3-hydroxypropanoic acid
Identifiers
CAS number	56-45-1 Y, 302-84-1 Y, 312-84-5 Y
PubChem	617
ChemSpider	5736 (L-form) Y, 597
UNII	452VLY9402 Y
EC-number	206-130-6
DrugBank	DB00133
ChEBI	CHEBI:17115 Y
ChEMBL	CHEMBL11298 Y
IUPHAR ligand	726
Jmol-3D images	Image 1
SMILES C([C@@H](C(=O)O)N)O
InChI InChI=1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1 Y Key: MTCFGRXMJLQNBG-REOHCLBHSA-N Y InChI=1/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)
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
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
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[link]

(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.^{[citation needed]}

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).^[4]

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.^[5]

Production[link]

Industrially, L-serine is produced by fermentation, with an estimated 100-1000 tonnes per year produced.^[6] In the laboratory, racemic serine can be prepared from methyl acrylate via several steps:^[7]

Biological function[link]

Metabolic[link]

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[link]

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[link]

D-Serine, synthesized in the brain by serine racemase from L-serine (its enantiomer), serves as both a neurotransmitter and a gliotransmitter by activating 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.^[8]

See also[link]

• Serine aggregation properties in Serine octamer clusters

References[link]

Raphael Mechoulam
Raphael Mechoulam
Born	1930 Sofia, Bulgaria
Residence	Jerusalem
Citizenship	Israel
Fields	Medicinal Chemistry, Natural Products
Institutions	Weizmann Institute of Science, Rockefeller University, Hebrew University of Jerusalem
Doctoral advisor	Prof. Franz Sondheimer
Known for	Total synthesis of tetrahydrocannabinol, major contributions to the chemistry of cannabinoids and discovery of endocannabinoids

Raphael Mechoulam (Hebrew: רפאל משולם‎) (born 1930) is an Israeli professor of Medicinal Chemistry and Natural Products at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of Δ⁹-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.

Early life and education[link]

Raphael Mechoulam was born in Sofia, Bulgaria on November 5, 1930. His father was a physician and head of a local hospital, while his mother "who had studied in Berlin, enjoyed the life of a well-to-do Jewish family". He attended an "American Grade School" until his parents were forced to leave their hometown because of anti-semitic laws and his father was subsequently sent to a concentration camp, from which he survived. After the communist takeover of hitherto pro-German Bulgaria in 1944 he studied chemical engineering, which he "disliked." In 1949 his family immigrated to Israel where he later studied chemistry. He gained his first research experience in the Israeli Army working on insecticides. He finished his PhD thesis on the chemistry of steroids under the supervision of Prof. Franz Sondheimer in 1950s. After a postdoctoral stay at the Rockefeller Institute with Prof. S. William Pelletier he became a junior member at the Weizmann Institute of Science.

Academic career[link]

Raphael Mechoulam, while being a junior member at the Weizmann Institute of Science, succeeded in the isolation, structure elucidation and total synthesis of Δ⁹-tetrahydrocannabinol, the main active principle of marijuana. He later became a full professor for medicinal chemistry at the Hebrew University of Jerusalem where he established the "Department of Natural Products". His major scientific interest is the chemistry and pharmacology of cannabinoids. He and his research group succeeded in the total synthesis of the major plant cannabinoids Δ⁹-tetrahydrocannabinol, cannabidiol, cannabigerol and various others. Another research project initiated by him led to the isolation of the first described endocannabinoid anandamide which was isolated and characterized by two of his postdoctoral researchers, Lumír Ondřej Hanuš and William Devane. Another endogenous cannabinoid, 2-AG, was soon discovered by Shimon Ben-Shabat, one of his PhD students. He published more than 350 scientific articles.

Awards and honours[link]

Mechoulam was awarded several prizes, including the Heinrich Wieland Prize.

Somach Sachs Prize for “best research by a scientist below 35 at the Weizmann Institute”, 1964.

Distinguished Visiting Professorship, Ohio State University, Columbus, Ohio, 1982-1983.

International Biannual Cannabis meeting (held in Colymbari, Crete), 1990, dedicated to R.M.

Pharmacology, Biochemistry and Behavior. Nov. 1991 issue dedicated to R.M. for achievements in the cannabinoid field.

Kolthof Prize in Chemistry, 1994, The Technion, Haifa.

Elected, Member Israel Academy of Sciences, 1994.

Ulf von Euler Lecture in Physiology Karolinska Institute. Stockholm, Sweden, 1994

Hanf prize, Germany, 1997, for “the discovery of THC and lasting research on Cannabis – anandamides”.

Hanus Medal, 1998, by Czech Chemical Society in recognition of contribution to cannabinoid chemistry.

David R. Bloom Prize, 1998, for “excellence in pharmaceutical research”, Hebrew University.

The International Cannabinoid Research Society established the "Raphael Mechoulam Annual Award in Cannabinoid Research" in 1999.

Israel Prize in Exact Sciences – chemistry, 2000.^[1][2] among others.

Ariens Award and Lecture. 2000. Dutch Pharmacological Society sponsored by Solvay Pharmaceuticals. Amsterdam.

Doctor Honoris Causa. Ohio State University, Columbus, Ohio, 2001.

Elected, Honorary Member, Israel Society of Physiology and Pharmacology, 2002.

Heinrich Wieland Prize, endowed by Boehringer-Ingelheim, to promote research on “lipids and related substances in the fields of Chemistry, Biochemistry, Physiology, and Clinical Medicine”, Germany, 2004.

Henrietta Szold Prize for achievements in medical research, Tel-Aviv Municipality, June 2005

Doctor Honoris Causa, Complutense University, Madrid, 2006

ECNP (European College of Neuropsychopharmaclogy) Lifetime Achievement Award, Paris, 2006.

Medal, Palacky University, for studies on materials with biological activity, Olomouc, The Czech State, September, 2008.

Israel Chemical Society Prize for excellence in research, Feb. 2009.

He is an elected member of the Israel Academy of Sciences and Humanities.

References[link]

Further reading[link]

• Mechoulam R (June 2007). "Conversation with Raphael Mechoulam". Addiction (Abingdon, England) 102 (6): 887–93. DOI:10.1111/j.1360-0443.2007.01795.x. PMID 17523982. 
• "School of Pharmacy - Prof. Mechoulam". http://pharmacy.huji.ac.il/eng/staff_win.asp?id=66. 

Podcasts[link]

• A podcast (open access) of an interview with Raphael Mechoulam, recorded by Steve Alexander for the British Journal of Pharmacology on the occasion of his 80th Birthday in November 2010

See also[link]

• List of Israel Prize recipients
• Tetrahydrocannabinol
• 2-Arachidonoylglycerol
• Anandamide
• Cannabidiol