por Cysteine (Cys, C) is one of the 22 amino acids found in nature as part of the polypeptide chains that make up the proteins of living beings. It is essential for the stability of the tertiary structures of proteins, as it helps in the formation of intramolecular disulfide bridges.
Just as it is true for other amino acids such as alanine, arginine, asparagine, glutamate and glutamine, glycine, proline, serine and tyrosine, humans are capable of synthesizing cysteine, so this is not considered an essential amino acid.
Despite this, and given that the synthesis rates do not always supply the body’s requirements, some authors describe cysteine as a «conditionally» essential amino acid.
This amino acid was named for «cystine», a component of gallstones discovered in 1810, whose name was coined in 1832 by A. Baudrimont and F. Malaguti. A few years later, in 1884, E. Baumann discovered that cysteine was the product of cystine reduction.
After the work carried out by Bauman, in 1899, it was determined that cysteine is the main constituent of the protein that makes up the horns of various animals, which suggested its possible use for the synthesis of polypeptides.
It is now known that body cysteine comes from food, from protein recycling, and from endogenous synthesis, which occurs mainly in hepatocytes.
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Characteristics
Cysteine has a molecular weight of 121.16 g/mol and is, along with leucine, isoleucine, valine, phenylalanine, tryptophan, methionine, and tyrosine, among the most hydrophobic amino acids.
It belongs to the group of uncharged polar amino acids and, like other amino acids, it can be degraded by alkaline hydrolysis at high temperatures.
Like tryptophan, serine, glycine, and threonine, cysteine is a metabolic precursor for gluconeogenesis and ketogenesis (ketone body formation).
This amino acid exists as part of the peptide sequence of proteins, but it can also be found free in blood plasma as homogeneous (cystine, a derivative) or mixed disulfides, composed of the homocysteine-cysteine form.
The main difference between free cysteine and that found in the protein structure is that the former is in a highly oxidized redox state, while the latter is usually quite reduced.
Structure
As with the rest of the amino acids described to date, cysteine has a central carbon atom, which is chiral and is known as α carbon.
Four different chemical species are attached to this carbon atom:
– an amino group (-NH3+)
– a carboxyl group (-COO-)
– a hydrogen atom and
– a substituent (-R).
The substituent group is the one that gives the identity to each amino acid and that of cysteine is characterized by containing a sulfur atom as part of a thiol or sulfhydryl group (-CH2-SH).
It is this group that allows it to participate in the formation of intra- and intermolecular disulfide bridges. Since it is a nucleophile, it can also participate in substitution reactions.
In fact, this cysteine side chain can be modified to form two compounds known as «selenocysteine» and «lanthionine.» The first is an amino acid that also participates in the formation of proteins and the second is a non-protein amino acid derivative.
The cysteine thiol group is also characterized by its high affinity for silver and mercury ions (Ag+ and Hg2+).
functions
The main functions of cysteine in living organisms have to do with its participation in the formation of proteins. Specifically, cysteine participates in the establishment of disulfide bridges, which are essential for the formation of the tertiary protein structure.
Furthermore, this amino acid is not only useful for protein synthesis, but is also involved in the synthesis of glutathione (GSH) and provides the reduced sulfur for methionine, lipoic acid, thiamine, coenzyme A (CoA), molybdopterin (a cofactor) and other compounds with biological importance.
Under conditions of excessive amounts of sulfur amino acids, cysteine and other related amino acids can be used for the production of pyruvate and inorganic sulfur. Pyruvate manages to be redirected towards the gluconeogenic route, serving for the production of glucose.
Keratins, which are one of the most abundant types of structural proteins in the animal kingdom, are rich in cysteine residues. For example, sheep’s wool contains more than 4% sulfur from this amino acid.
Cysteine also participates in many oxidation-reduction reactions, which is why it is part of the active site of some enzymes.
By reacting with glucose, this amino acid generates reaction products that introduce attractive tastes and aromas to some culinary preparations.
Biosynthesis
The biosynthesis of amino acids in the human body and that of other animals (mammals and non-mammals) takes place in a tissue- and cell-specific manner; it is a process that requires energy and is usually separated between different organs.
The liver is one of the main organs involved in the synthesis of most non-essential amino acids, regardless of the species considered.
In this, not only cysteine is synthesized, but also aspartate, asparagine, glutamate and glutamine, glycine, serine, tyrosine and others from their specific amino acid precursors.
In 1935, Erwin Brand determined that cysteine, in mammals, is naturally synthesized from methionine, which occurs exclusively in liver tissue.
This process can occur by a «transmethylation» of methionine, where the methyl groups are transferred to choline and creatine. However, cysteine can also be formed from methionine thanks to trans-sulfurization.
Subsequently it was shown that, in addition to methionine, some synthetic compounds such as N-acetyl cysteine, cysteamine and cystamine, are useful precursors for cysteine synthesis.
In the case of N-acetyl cysteine, it is taken up by cells, where it is converted to cysteine by a deacetylase enzyme in the cytosol.
Synthesis mechanism
The best-known mechanism for the synthesis of cysteine from methionine is that of trans-sulfurization. This occurs mainly in the liver, but has also been determined in the intestine and pancreas.
This occurs from homocysteine, a compound derived from the amino acid methionine; and the first reaction of this biosynthetic pathway is a condensation catalyzed by the enzyme cystathionine β-synthase (CBS).
This enzyme represents the «commitment» step of the pathway and condenses a homocysteine with a serine residue, another protein amino acid, producing cystathionine. Subsequently, this compound is «cut» or «cleaved» by the enzyme cystathionase, which leads to the release of cysteine.
The regulation of CBS enzymatic activity is mediated by the availability of methionine and by the redox state of the cell where this process occurs.
Through the cysteine synthesis pathway, cells can handle excess methionine, since its conversion to cysteine is an irreversible process.
Cysteine synthesis in plants and microorganisms
In these organisms, cysteine is synthesized mainly from inorganic sulfur, which is the most abundant source of usable sulfur in the aerobic biosphere.
This is taken up, enters the cells and is then reduced to sulfur (S2-), which is incorporated into cysteine in a similar way to what happens with ammonium in the synthesis of glutamate or glutamine.
metabolism and degradation
Cysteine catabolism occurs mainly in liver cells (hepatocytes), although it can also occur in other cell types such as neurons, endothelial cells, and smooth muscle cells of the body’s vasculature.
Certain defects in cysteine catabolism produce a hereditary disease known as “cystinuria”, characterized by the presence of cystine stones in the kidneys, bladder and ureter.
Cystine is an amino acid derived from cysteine and stones are formed by the union of two molecules of these through their sulfur atoms.
Part of the metabolism of cysteine results in the formation of scientinsulfinic acid, from which taurine, a non-protein amino acid, is formed. The reaction is catalyzed by the enzyme cysteine dioxygenase.
Additionally, cysteine can be oxidized by formaldehyde to produce N-formyl cysteine, whose further processing can lead to the formation of «mercapturate» (product of the condensation of cysteines with aromatic compounds).
In animals, cysteine is also used, as well as glutamate and glutamine, for the synthesis of coenzyme A, glutathione (GSH), pyruvate, sulfate, and hydrogen sulfide.
One of the methods for the conversion of cysteine to pyruvate occurs in two steps: the first involves removal of the sulfur atom and the second a transamination reaction.
The kidneys are responsible for the excretion of sulfates and sulfites derived from the metabolism of sulfur compounds such as cysteine, while the lungs exhale sulfur dioxide and hydrogen sulfide.
glutathione
Glutathione, a molecule made up of three amino acid residues (glycine, glutamate and cysteine) is a molecule that is present in plants, animals and bacteria.
It has special properties that make it an excellent redox buffer, as it protects cells from different types of oxidative stress.
Foods rich in cysteine
Cysteine is found naturally in sulfur-containing foods such as (yellow) egg yolks, red bell peppers, garlic, onions, broccoli, cauliflower, kale and Brussels sprouts, watercress, and mustard greens.
It is also present mostly in foods rich in protein such as meats, legumes and dairy products, among which are:
– Beef, pork, chicken and fish
– Oatmeal and lentils
– Sunflower seeds
– Yogurt and cheese
Benefits of cysteine intake
Its intake is considered to prevent hair loss and stimulate its growth. In the food industry it is widely used as an agent for improving bread dough and also to «reproduce» flavors similar to meat.
Other authors have reported that the intake of dietary supplements or foods rich in cysteine decreases the biochemical lesions caused by the excessive consumption of foods contaminated with metallic elements, since it participates in «chelation» reactions.
Some nutritional supplements related to cysteine are used by human beings…