Serine (symbol Ser or S)  is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated – form in physiological conditions), and a side chain consisting of a hydroxymethyl group (see hydroxyl), classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC.
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 by Emil Cramer . Its name is derived from the Latin for silk, sericum. Serine's structure was established in 1902.
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). 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 CO2, NH4+, and mTHF in a reaction catalyzed by glycine synthase.
D-Serine, synthesized in neurons 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 (NR1) of the NMDA-type glutamate receptor (NMDAR). For the receptor to open, glutamate and either glycine or D-serine must bind to it; in addition a pore blocker must not be bound (e.g. Mg2+ or Zn2+). In fact, D-serine is a more potent agonist at the glycine site on the NMDAR than glycine itself.
D-serine was thought to exist only in bacteria until relatively recently; it was the second D amino acid discovered to naturally exist in humans, present as a signaling 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.
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.
Serine deficiency disorders are rare defects in the biosynthesis of the amino acid L-serine. At present three disorders have been reported: 3-phosphoglycerate dehydrogenase deficiency, 3-phosphoserine phosphatase deficiency and Phosphoserine aminotransferase deficiency. These enzyme defects lead to severe neurological symptoms such as congenital microcephaly and severe psychomotor retardation and in addition in patients with 3-phosphoglycerate dehydrogenase deficiency to intractable seizures. These symptoms respond to a variable degree to treatment with L-serine, sometimes combined with glycine.  Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, as well as for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).
D-Serine is being studied in rodents as a potential treatment for schizophrenia and L-serine is in a FDA-approved human clinical trial as a possible treatment for Amyotrophic Lateral Sclerosis ALS (ClinicalTrials.gov identifier: NCT01835782). 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 cerebrospinal fluid of probable AD patients.
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