10 julio, 2024

Serine: characteristics, functions, metabolism, foods

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

In accordance with 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.

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

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

The rate of serine synthesis 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, as the permeability of the blood-brain barrier decreases in the adult brain, potentially causing 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.

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

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Characteristics and structure

All amino acids have as a basic structure a carboxyl group and an amino group attached to the same carbon atom; however, these are differentiated 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 on 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 single carbon atom in its R group, which is attached to the OH group, is known as the γ-carbon.

Classification

Serine is classified within the group of uncharged polar amino acids. The members of this group are amino acids that are highly soluble in water, 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.

Cysteine, asparagine and glutamine are also grouped within the group of uncharged polar amino acids. All of these have a polar group in their R chain, however, this group is not ionizable and at pH 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, this can be found as D- or L-serine, the latter being synthesized exclusively by nervous system cells known as astrocytes.

The α carbons of amino acids are chiral carbons, since they have four different substituents attached, which means 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 with the letter D or L since experimentally the solutions of these amino acids rotate the plane of polarized light in opposite directions.

The 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 vesicle exchange between neurons to occur, which is why some authors propose that both serine isoforms are actually essential amino acids for neurons.

functions

Serine’s OH group on its R chain makes it a good nucleophile, so it is key to the activity of many enzymes with serines at their active sites. Serine is one of the necessary substrates for the synthesis of NADPH and glutathione nucleotides.

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 the subsequent proliferation of cancer cells.

Selenocysteine ​​is part of the 22 basic amino acids and is only obtained as a derivative of serine. This amino acid has been observed only in some proteins, contains selenium instead of sulfur bound to cysteine, and 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 from 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, the synthesis occurs by a phosphorylation pathway involving 3-phosphoglycerate, a glycolytic intermediate.

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

Other important organs as far as serine synthesis is concerned are the liver, kidneys, testicles and spleen. Enzymes that synthesize serine by pathways other than phosphorylation are found only in the liver and kidneys.

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

Metabolism

It is now 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 this 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 glucose minimal media.

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

foods rich in serine

All foods with high protein concentrations 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 present a deficient phenotype regarding the mechanisms of synthesis of serine and glycine, therefore, they need to ingest concentrated food supplements for both amino acids.

In addition, commercial brands specialized 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 weight lifters.

Related diseases

The malfunction of the enzymes involved in the biosynthesis of serine can cause serious pathologies. By decreasing the concentration of serine in the blood plasma and cerebrospinal fluid, it can lead to 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, present with intrauterine growth retardation, congenital microcephaly, cataracts, seizures, and severe neurodevelopmental delay.

References

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.
Ichord, RN, & Bearden, DR (2017). Perinatal metabolic encephalopathies. In Swaiman’s Pediatric Neurology (pp. 171-177). Elsevier.
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
Nelson, DL, Lehninger, AL, & Cox, MM (2008). Lehninger principles of biochemistry. macmillan.
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.
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.

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