SERINE: CHARACTERISTICS, FUNCTIONS, METABOLISM, FOOD - BIOLOGY - 2025

The serine is one of 22 basic amino acids, although this is not classified as an essential amino acid for humans and other animals, since it is synthesized by the human body.

According to the three letter nomenclature, serine is described in the literature as Ser (S in the single letter code). This amino acid participates in a large number of metabolic pathways and has polar characteristics, but has no charge at neutral pH.

Representation of the amino acid structure Serine (Source: Paginazero at it.wikipedia via Wikimedia Commons)

Many enzymes important for cells have abundant concentrations of serine residues in their active sites, which is why this amino acid has multiple physiological and metabolic implications.

Serine, among many of its functions, participates as a precursor and scaffold molecule in the biosynthesis of other amino acids such as glycine and cysteine ​​and is part of the structure of sphingolipids present in cell membranes.

The rate of synthesis of serine varies in each organ and, in addition, it changes according to the stage of development in which the individual is.

Scientists have proposed that L-serine concentrations in brain tissue increase with age, since the permeability of the blood-brain barrier decreases in the adult brain, which can cause severe brain disorders.

L-serine is known to be vital for the biosynthesis of neurotransmitters, phospholipids, and other complex macromolecules, as it provides the precursors for these multiple metabolic pathways.

Several studies have shown that supplying L-serine supplements or concentrates to certain types of patients improves glucose homeostasis, mitochondrial function and reduces neuronal death.

Characteristics and structure

All amino acids have as their basic structure a carboxyl group and an amino group bound to the same carbon atom; However, these differ from each other by their side chains, known as R groups, which can vary in size, structure and even in their electrical charge.

Serine contains three carbon atoms: a central carbon attached, on the one hand, to a carboxyl group (COOH) and, on the other, to an amino group (NH3 +). The other two bonds of the central carbon are occupied by a hydrogen atom and by a CH2OH group (R group), characteristic of serine.

The central carbon to which the amino and carboxyl groups of amino acids are attached is known as the α-carbon. The other carbon atoms in the R groups are designated by the letters of the Greek alphabet.

In the case of serine, for example, the only carbon atom in its R group, which is attached to the OH group, is known as γ-carbon.

Classification

Serine is classified within the group of uncharged polar amino acids. The members of this group are highly water soluble amino acids, that is, they are hydrophilic compounds. In serine and threonine, hydrophilicity is due to their ability to form hydrogen bonds with water through their hydroxyl (OH) groups.

Within the group of uncharged polar amino acids, cysteine, asparagine and glutamine are also grouped. All of these have a polar group in their R chain, however, this group is not ionizable and at pHs close to neutrality they cancel their charges, producing a compound in the form of a "zwitterion".

Stereochemistry

The general asymmetry of amino acids makes the stereochemistry of these compounds of vital importance in the metabolic pathways in which they participate. In the case of serine, it can be found as D- or L-serine, the latter being synthesized exclusively by cells of the nervous system known as astrocytes.

The α carbons of amino acids are chiral carbons, since they have four different substituents attached, which generates that there are at least two distinguishable stereoisomers for each amino acid.

A stereoisomer is a mirror image of a molecule, that is, one cannot be superimposed on the other. They are denoted by the letter D or L since experimentally the solutions of these amino acids rotate the plane of polarized light in opposite directions.

L-serine that is synthesized in cells of the nervous system serves as a substrate to synthesize glycine or D-serine. D-serine is one of the most important elements for the exchange of vesicles between neurons to occur, which is why some authors propose that both isoforms of serine are, in fact, essential amino acids for neurons.

Features

The OH group of serine in its R chain makes it a good nucleophile, so it is key to the activity of many enzymes with serines in their active sites. Serine is one of the substrates required for the synthesis of nucleotides NADPH and glutathione.

L-serine is essential for the development and proper functioning of the central nervous system. Studies have shown that exogenous delivery of L-serine in low doses to hippocampal neurons and Purkinje cells in vitro improves their survival.

Various studies of cancer cells and lymphocytes have found that serine-dependent carbon units are necessary for the excessive production of nucleotides, as well as for the subsequent proliferation of cancer cells.

Selenocysteine ​​is one of the 22 basic amino acids and is obtained only as a derivative of serine. This amino acid has only been observed in some proteins, it contains selenium instead of sulfur bound to cysteine ​​and it is synthesized starting from an esterified serine.

Biosynthesis

Serine is a non-essential amino acid, since it is synthesized by the human body. However, it can be assimilated from the diet of different sources such as proteins and phospholipids, mainly.

Serine is synthesized in its L form through the conversion of a glycine molecule, a reaction mediated by a hydroxymethyl-transferase enzyme.

It is known that the main site of L-serine synthesis is in astrocytes and not in neurons. In these cells, synthesis occurs by a phosphorylation pathway in which 3-phosphoglycerate, a glycolytic intermediate, participates.

Three enzymes act in this pathway: 3-phosphoglycerate dehydrogenase, phosphoserine-transferase and phosphoserine-phosphatase.

Other important organs when it comes to serine synthesis are the liver, kidneys, testes, and spleen. Enzymes that synthesize serine by pathways other than phosphorylation are only found in the liver and kidneys.

One of the first known serine synthesis routes was the catabolic pathway involved in gluconeogenesis, where L-serine is obtained as a secondary metabolite. However, the contribution of this route to body serine production is low.

Metabolism

Currently it is known that serine can be obtained from carbohydrate metabolism in the liver, where D-glyceric acid, 3-phosphoglyceric acid and 3-phosphohydroxypyruvic acid are produced. Thanks to a transamination process between 3-hydroxy pyruvic acid and alanine, serine is produced.

Experiments carried out with rats radioactively labeling carbon 4 of glucose, have concluded that this carbon is effectively incorporated into the carbon skeletons of serine, suggesting that said amino acid has a three-carbon precursor probably from pyruvate.

In bacteria, the enzyme L-serine-deaminase is the main enzyme in charge of metabolizing serine: it converts L-serine into pyruvate. This enzyme is known to be present and active in E. coli cultures grown in minimal media with glucose.

It is not known for sure what is the real function of L-serine-deaminase in these microorganisms, since its expression is induced by mutational effectors that damage DNA by ultraviolet radiation, by the presence of nalidixic acid, mitomycin and others. from which it follows that it must have important physiological implications.

Foods rich in serine

All foods with high concentrations of protein are rich in serine, mainly eggs, meat and fish. However, this is a non-essential amino acid, so it is not strictly necessary to ingest it, since the body is capable of synthesizing it on its own.

Some people suffer from a rare disorder, since they have a phenotype with deficiency regarding the synthesis mechanisms of serine and glycine, therefore, they need to ingest concentrated food supplements for both amino acids.

In addition, commercial brands specializing in the sale of vitamin supplements (Lamberts, Now Sport and HoloMega) offer phosphatidylserine and L-serine concentrates to increase the production of muscle mass in highly competitive athletes and weightlifters.

Related diseases

The malfunction of the enzymes involved in the biosynthesis of serine can cause serious pathologies. By decreasing the concentration of serine in blood plasma and cerebrospinal fluid, it can cause hypertonia, psychomotor retardation, microcephaly, epilepsy, and complex disorders of the central nervous system.

Currently it has been discovered that serine deficiency is involved in the development of diabetes mellitus, since L-serine is necessary for the synthesis of insulin and its receptors.

Babies with defects in serine biosynthesis are neurologically abnormal at birth, have intrauterine growth retardation, congenital microcephaly, cataracts, seizures, and severe neurodevelopmental delay.

References

1. Elsila, JE, Dworkin, JP, Bernstein, MP, Martin, MP, & Sandford, SA (2007). Mechanisms of amino acid formation in interstellar ice analogs. The Astrophysical Journal, 660 (1), 911.
2. Ichord, RN, & Bearden, DR (2017). Perinatal metabolic encephalopathies. In Swaiman's Pediatric Neurology (pp. 171-177). Elsevier.
3. Mothet, JP, Parent, AT, Wolosker, H., Brady, RO, Linden, DJ, Ferris, CD,… & Snyder, SH (2000). D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proceedings of the National Academy of Sciences, 97 (9), 4926-4931
4. Nelson, DL, Lehninger, AL, & Cox, MM (2008). Lehninger principles of biochemistry. Macmillan.
5. Rodríguez, AE, Ducker, GS, Billingham, LK, Martinez, CA, Mainolfi, N., Suri, V.,… & Chandel, NS (2019). Serine Metabolism Supports Macrophage IL-1β Production. Cell metabolism, 29 (4), 1003-1011.
6. Tabatabaie, L., Klomp, LW, Berger, R., & De Koning, TJ (2010). L-serine synthesis in the central nervous system: a review on serine deficiency disorders. Molecular genetics and metabolism, 99 (3), 256-262.