Serine

Not to be confused with Sarin.

For the French wine grape, see Serine (grape).

Serine

Names
IUPAC name Serine
Other names 2-Amino-3-hydroxypropanoic acid
Identifiers
CAS Number	56-45-1 (L-isomer) Y 302-84-1 Y 312-84-5 (D-isomer) Y
ChEBI	CHEBI:17115 Y
ChEMBL	ChEMBL11298 Y
ChemSpider	5736 (L-form) Y 597 Y
DrugBank	DB00133 Y
EC Number	206-130-6
IUPHAR/BPS	726
Jmol 3D model	Interactive image
PubChem	617
UNII	452VLY9402 Y
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)
SMILES C([C@@H](C(=O)O)N)O
Properties
Chemical 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 (475 °F; 519 K) decomposes
Solubility in water	soluble
Acidity (pKa)	2.21 (carboxyl), 9.15 (amino)
Supplementary data page
Structure and properties	Refractive index (n), Dielectric constant (εr), etc.
Thermodynamic data	Phase behaviour solid–liquid–gas
Spectral data	UV, IR, NMR, MS
Y verify (what is YN ?)
Infobox references

Serine (abbreviated as Ser or S) encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH⁺
₃ form under biological conditions), a carboxyl group (which is in the deprotonated –COO⁻
form under biological conditions), and a side chain hydroxyl group, classifying it as a polar amino acid. It is non-essential in humans, meaning the body can synthesize it.

Occurrence

(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.

Biosynthesis

The biosynthesis of serine starts with the oxidation of 3-phosphoglycerate (an intermediate from glycolysis) to 3-phosphohydroxypyruvate and NADH by phosphoglycerate dehydrogenase (EC 1.1.1.95). Reductive amination (transamination) of this ketone by phosphoserine transaminase (EC 2.6.1.52) yields 3-phosphoserine (O-phosphoserine) which is hydrolyzed to serine by phosphoserine phosphatase (EC 3.1.3.3).

In bacteria such as E. coli these enzymes are encoded by the genes serA (EC 1.1.1.95), serC (EC 2.6.1.52), and serB (EC 3.1.3.3).

Serine biosynthesis

Glycine biosynthesis: Serine hydroxymethyltransferase (SHMT = serine transhydroxymethylase) also catalyzes the reversible conversions of L-serine to glycine (retro-aldol cleavage) and 5,6,7,8-tetrahydrofolate to 5,10-methylenetetrahydrofolate (mTHF) (hydrolysis). SHMT is a pyridoxal phosphate (PLP) dependent enzyme. Glycine can also be formed from CO_2, NH₄⁺, and mTHF in a reaction catalyzed by glycine synthase.

Synthesis and industrial production

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

Biological function

Metabolic

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

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 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

D-Serine, synthesized in the brain by serine racemase from L-serine (its enantiomer), serves as a neuromodulator 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 (NMDAR). 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. Apart from central nervous system, D-serine plays a signaling role in peripheral tissues and organs such as cartilage, kidney and corpus cavernosum.

Gustatory sensation

L-Serine is sweet with minor umami and sour tastes at high concentration.

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

Research for therapeutic use

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. A 2011 meta-analysis found adjunctive sarcosine to have a medium effect size for negative and total symptoms. D-Serine has also been described as a potential biomarker for early Alzheimer's disease (AD) diagnosis, due to a relatively high concentration of it in the CSF of probable AD patients.

See also

• Serine aggregation properties in Serine octamer clusters

External links

• Serine MS Spectrum