Myoglobin

Myoglobin is a cytoplasmic hemoprotein composed by a single polypeptide chain of 154 amino acids. It is expressed solely in cardiac myocytes and oxidative skeletal muscle fibers. Myoglobin was so named because of its functional and structural similarity to hemoglobin. Like hemoglobin, myoglobin binds reversibly to O2 and thus may facilitate the transport of O2 from red blood cells to the mitochondria during periods of increased metabolic activity or serve as an O 2 reservoir during hypoxia or anoxia.The structure of myoglobin was first delineated by John Kendrew more than 40 years ago and subsequent work has shown that it is a polypeptide chain consisting of eight α-helices. It binds oxygen to its heme residue, a porphyrin ring with an iron ion. The polypeptide chain is folded and packs the heme prosthetic group, positioning it between two histidine, His64 and His93 residues. The iron ion interacts with six ligands, four of which are supplied by the nitrogen atoms of the four pyrrhols and share a common plane. The side chain imidazole of His93, provides the fifth ligand, stabilizing the heme group and slightly displacing the iron ion out of the heme plane. The position of the sixth ligand, in deoximoglobin, serves as the binding site for O2, as well as for other potential ligands, such as CO or NO. When O2 binds, the iron ion, it is partially drawn back toward the porphyrin plane. Although this shift is of little importance in the function of monomeric myoglobin, it provides the basis for the conformational changes that underlie the allosteric properties of tetrameric hemoglobin. In addition, studies using X-ray diffraction and xenon binding techniques have identified four highly conserved internal cavities within the myoglobin molecule that can help target molecules to bind to the heme residue.Related to its role as an O2 reservoir, myoglobin also functions as an intracellular pO2 buffer (partial pressure of O2). Similarly to the role of creatine phosphokinase, which works to buffer ATP concentrations when muscle activity increases, myoglobin works to buffer O2 concentrations. As a result, the intracellular concentration of O2 remains relatively constant and homogeneous, despite increases in O2 flow from the capillaries to the mitochondria, induced by physical activity.

Text written by:

Ana Rita Cardoso

João Faria

Joel Mateus

Pedro Desport
.

Insulin

Insulin is a polypeptide hormone produced, stored and secreted in Beta cells of the islets of Langerhans, in the pancreas (in a histological section it is seen that they occupy the central part). It is an anabolic hormone that acts at the level of the liver, adipose tissue and with influence in the brain.
This protein has two polypeptide chains, with 21 amino acids in the A chain and 30 in the B chain, joined by disulfide bonds, which gives a greater stability and a correct folding. It begins to be produced in the form of pre-pro-insulin which, by action of the peptidase is cleaved to form the proinsulin. The proteolytic cleavage of peptide C forms the two chain bioactive insulin, which is stored in secretory granules for subsequent insulin secretion.Its main function is to regulate blood glucose levels in a context of hyperglycemia. In this way, glucose acts as a biochemical signal that triggers its secretion. Thus, when carbohydrate-containing foods are absorbed, glucose is metabolized to ATP and this in turn triggers insulin secretion. Protein-protein interactions and phosphorylations are used to transmit the signal. In adipose tissue and muscle, the binding of insulin to membrane receptors triggers the displacement of GLUT4-rich vesicles that fuse with the membrane, increasing cell uptake, being an insulin-dependent transport.
On the other hand, in the liver, insulin activates the enzyme glycokinase, which is responsible for the conversion of glucose into glucose-6-phosphate; Guarantees an intracellular concentration of glucose lower than the extracellular concentration and, therefore, a gradient of glucose concentration favorable to its entry into these cells, through the GLUT-2 transporter, following metabolization by glycolysis, Krebs and the respiratory chain to produce ATP. Thus, after food intake, glucose is absorbed into the intestines and is released into the bloodstream, causing blood concentrations to rise, leading to transient hyperglycemia. The pancreas releases insulin to lower glucose concentration, allowing glucose to be consumed by the cells, as well as stimulating the storage of glucose in the liver in the form of glycogen; The liver also metabolize glucose into triacylglycerols, transported as VLDL to be stored in adipose tissue, which are useful reserves in fasting situations. Signal transmission ceases, at meal time, by dephosphorylation of the insulin receptor by protein tyrosine phosphatase.
In summary, insulin stimulates glycogenesis, fatty acid synthesis and glycolysis and inhibits antagonistic pathways: glycogenolysis, fatty acid degradation and hepatic gluconeogenesis. It also stimulates protein synthesis. It has action on inherent enzymes as well as effects on gene transcription. It also acts on specific receptors in the hypothalamus to inhibit the act of eating, thus regulating feeding and energy conservation.
Inborn errors of beta cell metabolism can produce excessive or defective production of insulin by gene mutations (GCK), Kir 6.2 alterations, or insulin synthesis transcription factors, respectively. Increased glucose leads to increased osmotic pressure, glycation of proteins and formation of reactive oxygen species (EROS).
Diabetes is the metabolic disease characterized by increased blood sugar: It may be Type I - in which the body stops producing insulin by destroying the B cells of the pancreas. It is important to check for symptoms of polydipsia, fruity aroma breathing, blood glucose and blood ketones levels. Essential therapies focus on insulin therapy, fluid replacement, replacement of electrolytes and nourishment. In turn, in Type II diabetes, the cells do not produce enough insulin to lower the concentration of gucose or there is a condition of insulin resistance. Adipocytes, myocytes and hepatocytes do not respond correctly. It presents symptoms similar to type I but more gradual. It is necessary to test for fasting blood glucose and for abnormal levels to continue the investigation for glycemic curve; glycated hemoglobin, control alcohol consumption, etc.
They can lead to complications such as diabetic retinopathy, atherosclerosis, diabetic nephropathy, neuropathy, myocardial infarction/stroke, infections - leucocytes less effective in hyperglycemia, hypertension and oxidation of blood vessels. There are currently several drugs on the market that address problems with insulin, as well as different types of injectable insulin depending on the cause of the disease and the purpose of action.

Text written by:

Denilson Araújo

Prescília Sampa

Solange da Costa

.

Hemoglobin

For higher animals, simple diffusion mechanisms in body fluids are not an efficient way to meet the oxygenation needs of their tissues and cellular material. To the low area/volume ratio of these living beings, it is added the fact that O2 is a molecule that is essentially insoluble, which makes its transport even more difficult. The solution then passes through carrier proteins, associated with erythrocytes - hemoglobin, to which the following lines refer.Hemoglobin is an oligomeric protein and is generally a metalloprotein consisting of about 600 amino acids, arranged in 2 alpha chains and 2 paired beta chains in a quaternary globular structure. The four chains constitute the organic part of the molecule, and are attached to heme prosthetic groups (consisting of a porphyrin ring and a transition metal: Fe2+) which have affinity for the O2 molecules because of the electron configuration. It is the Fe2+ that assumes this function, always in its ferrous form, and the ferric form - Fe3+ - is not able to bind O2, being at the same time more unstable and prone to the formation of reactive species. Fe2+ has one O2 binding site and this bond as expected would be reversible to allow oxygen to be transported to where it is needed. Due to this binding, there is a change of color in human blood, from bright red when it is in its oxygenated form, to a more purplish tone in its venous phase. Some molecules such as CO2 and NO have a higher affinity for the heme group, "expelling" O2 molecules from erythrocytes, which explains their toxicity to the organism. 

Porphyrias are genetic diseases related to porphyrin of the heme group. Examples are acute intermittent porphyria and accumulation of uroporphyrogen I each with specific symptoms.
Concerning the coordinated transport of O2, CO2 and H+, the mechanism is as follows: 

O2 binds cooperatively to hemoglobin (this means that the bonds promote more bonds) and then the affinity of hemoglobin varies with pH. In an acidic environment, H+ and CO2 cause the release of O2 whereas in a basic medium, O2 causes the release of H+ and CO2. This is the so-called Bohr effect(reciprocal effect): CO2 + H2O <-> HCO3- + H+
The dead erythrocytes release the heme group generating: Fe3+ (which is recycled) and bilirubin (which is excreted in the liver). The latter may have a negative effect if released into the blood because it causes jaundice, or a positive antioxidant effect especially as an antioxidant of the membrane, because it collects two hydroperoxide radicals, having about 1/10 the efficiency of vitamin C.

Text written by:
Beatriz Ribeiro
Cláudia Campos
.

Glycogenin

The glycogenin is a protein whose main function is to be the initiator molecule of glycogen synthesis (glycogenesis), a process that allows the storage of glucose residues in the form of a polysaccharide. Glucose residues are added to glycogenin through α-1,4 bonds. The first step in the glycogen synthesis is indeed the synthesis of this protein. Each glycogen molecule is linked to a glycogenin by a glycosidic linkage which involves the first glucose residue of the chain and a tyrosine residue of glycogenin. The glycogenin designation stems from the fact that this protein is involved in the genesis of glycogen, by functioning as a primer in the formation of a new glycogen molecule.The glycogenin through its glucosyltransferase activity, binds covalently to itself a glucose molecule (from UDP-glucose - the active form of glucose). Then, the glycogenin forms a compact complex with glycogen synthase, the enzyme responsible for glycogen synthesis. After the addition of up to 7 more glucose residues (from UDP-glucose) mediated again by the activity of glucosyltransferase of glycogenin. Finally, glycogen synthase and branching enzyme enter in action, being glycogenin covalently linked to the unique reducing end of the glycogen molecule.
In humans there are two isoforms of glycogenin which can be expressed as glycogenin-1, having a molecular weight of 37 kD, and encoded by the GYG gene that is expressed mainly in muscle, or as glycogenin-2 having a molecular weight of 66 kDae encoded by GYG2 gene which is expressed mainly in the liver, cardiac muscle and other types of tissues except skeletal muscle

Disability glycogenin-1 (GYG1) - Mutation of the gene GYG1
A glycogenin-1 deficiency was detected in its gene, GYG1, which revealed a nonsense mutation in one allele and a missense mutation in another allele. A missense mutation results from inactivation of the autoglycosilation of glycogenin-1, which is required for the initiation of glycogen synthesis in muscle. The glycogenin-1 autoglycosilation occurs at Tyr195 by the action of glucose-1-O-tyrosine. A missense mutation of this residue results in inactivation of the autoglycosilation. However, it was also demonstrated that missense mutations affecting other residues of glycogenin 1-cause problems on autoglycosilation.
Phenotypic characteristics of skeletal muscle in a patient with this disorder are muscle glycogen depletion, mitochondrial proliferation and marked predominance of slow twitch amd oxidized muscle fibers. Mutations in glycogenin-1 gene GYG1 are also causes of cardiomyopathy and arrhythmia.

Text written by:

Daniela Marinheiro

Carla Marty

Maria Rocha

Marta Rodrigues

Rita Osório

.

Enolase

Enolase is an enzyme, more particularly, an active metalloenzyme. This enzyme belongs to the family of lyases, the hydro-lyases, breaking the carbon-oxygen bonds, and is present in all tissues and organisms involved in glycolysis or fermentation. The optimal pH of this enzyme is 6.5 in humans.Its main function is to intervene in the 9th step of glycolysis (the penultimate step in this metabolic pathway), a step in which occurs the dehydration of 2-phosphoglycerate (2-PG) in phosphoenolpyruvate (PEP), a product that will be used in the next and final step for the production of energy (ATP).
Enolase has three different isoforms: the ENO1 or alpha-enolase (in muscle tissue); ENO2 or gamma-enolase or neuro specific enolase (in neurons); ENO3 or beta-enolase (in skeletal muscle cells). Enolase has a molecular weight of about 100000 Daltons (depending on the isoform). In humans, the α-enolase has two antiparallel subunits, which have two domains that establish hydrophobic interactions. The subunits interact via salt bridges, involving arginine and glutamate.
The specific enolase to neurons is released in a wide variety of diseases, such as multiple sclerosis or stroke, or myocardial infarction.
In several medical experiments, it was employed enolase concentrations in samples in an attempt to diagnose certain conditions and its severity. Several studies demonstrated that different levels of enolase may also be associated with tumor growth or with the occurrence of myocardial infarction or stroke, so it was inferred that the levels of enolase serve as an indicative of the prognostic evaluation of victims of cardiac arrest.
Enolase inhibitors have been utilized in health care for the treatment and prevention various diseases, such as anti-trypanosome drugs and more recently as anticancer agents. Enolase can be inhibited by fluoride ion (F-). The fluoride forms a complex with magnesium and phosphate, which binds to the active center of the enzyme rather than the substrate 2-PG, preventing the conversion of 2-PG into PEP, decreasing the production of PEP and, consequently, ATP.
Intake of fluoride-containing water inhibits the catalytic activity of enolase of bacteria present in oral cavity (highly dependent on glycolysis due to the anaerobic environment), interrupting glycolysis and, thus, bacterial fermentation (decreased acid production), preventing the formation of dental caries.

Text written by:
Inês Carvalho
Junjie Lin
Maria Alves
Susana Pinto
.

Cytochrome c

Cytochromes were first described in 1884 by MacMunn as respiratory pigments. Later, in 1920, Keilin rediscovered these respiratory pigments and gave them the name of Cytochrome, classifying these heme proteins based on the lowest level of the cytochrome energy absorption position.Cytochrome c is a small protein with 104 amino acids located in the intermembrane space of mitochondria of all living beings who do aerobic respiration. Part of its chain is separated by a matrix protease when the polypeptide is inserted into the inner membrane, being anchored in a proper orientation.It is a heteroprotein (protein composed of amino acids and other chemical elements), which besides amino acids, has a heme group (cofactor)that is bound to the cysteines 14:17.It is a hydrophilic protein, highly soluble in water (solubility ~100g /L).The percentage of each type of amino acid present in the protein varies, depending on the species and it is related to their evolutionary proximity. The variation in the primary structure in different species, indirectly reveals their genetic differences since the code for the protein is written in the genes. This protein plays an important role in cellular respiration as it is an electron carrier between complexes III and IV, displacing them to an oxygen molecule (final acceptor), thereby converting molecular oxygen to two molecules of water. In this process, it occurs translocation of protons to the intermembrane space, which help the formation of a chemiosmotic potential used by the ATP synthase for the formation of ATP. It is also responsible for stimulating programmed cell death, or apoptosis, by activating the intrinsic pathway of the process. This leads to activation of caspase 9, which in turn activates caspases 3 and 7, and the target cell  dies by apoptosis. Finally, it also promotes the release of calcium stored in the endoplasmic reticulum, increasing the ion concentration in the cytosol.Regarding the formation of cytochromes, they suffer reversible changes in the iron oxidation number, changing between +2 and +3 in a cyclical process. There are three main groups of cytochromes, denominated by the letters a, b and c. They differ in the structure of the prosthetic group (side chain), leading to different absorption spectra, wherein the cytochrome c absorbs the shorter wavelengths.

Text written by:

Ana Ribeiro

João Esteves 

Maria Correia

Maria Melo

Video about protein structure

Catalase

Catalase, or hydroperoxidase, is an intracellular enzyme found in most organisms. This protein is found in the peroxisomes, glyoxisomes (plant peroxisome) and in the cytoplasm of prokaryotes. Catalase is an oxidoreductase, since it uses hydrogen peroxide (H2O2)both as an acceptor of electrons and as an electronic donor, decomposing it accordingly to this chemical reaction: 2H2O2 → 2H2O + O2.Although there are various known forms of this enzyme, it is commonly found in the form of a tetramer of 240 kDa, having four polypeptide chains in a quaternary structure. Each polypeptide chain binds a heme group that has an iron ion, which reacts with the hydrogen peroxide, decomposing the molecule. However, there are also some non-heme catalases, that is, instead of havin heme groups, they have one binuclear manganese center.
The toxic H2O2 is a product of the metabolism of our cells, produced, for example, during the peroxisomal β-oxidation of fatty acids, which requires a rapid conversion of it into a chemical species that is harmless the organism. Catalase has the highest known turnover number (kcat): the enzymes is able to decompose 40000000 H2O2 molecules per second! Catalase is also important for certain invading microorganisms, which is used as a defense system against some cells of our immune system whose action rely in the production of H2O2 as an antibacterial agent. Finally, this enzyme is associated with delayed aging mechanism connected to oxidative stress.
The reaction catalyzed by this enzyme is a dismutation reaction, i.e., the substrate acts as both reductant and oxidant agent. It is known that it occurs in two basic steps: H2O2 + Fe (III)-E → H2O + O = Fe (IV)-E and H2O2 + O = Fe (IV)-E → H2O + Fe (III)-E + O2. 

Fe-E represents the iron ion of the heme group, bound to the enzyme. Catalase is also capable of catalyzing the oxidation of other molecules such as formaldehyde, formic acid and certain alcohols. H2O2 + H2R → 2H2O + R, where R is the oxidized form of the molecule that undergoes the reaction. Metal ions (especially copper (II) and iron (II)) are non-competitive inhibitors, and cyanide and curare behave as competitive inhibitors.
Catalase is used also used in the textile industry to remove H2O2 from the tissues, and in some contact lens cleaning products, acting as an antibacterial agent. Currently, it has also been used in beauty masks, combining the enzyme with H2O2 to increase cellular oxygenation of the upper layers of the epidermis.
The so-called Catalase Test is used in microbiology and consists in the detection of catalase in bacteria, serving essentially to distinguish staphylococci and streptococci. In this test, peroxide is put in contact with a liquid microorganism culture to be tested if it appears bubbles (oxygen); if so, the organism is catalase-positive (has catalase if staphylococci), otherwise, it is designated catalase-negative (streptococci).

Text written by:
Ana Araújo
Inês Oliveira
Mariana Pires
José Cardoso

.

Video about the isoelectric point of a protein

Albumin

Albumin is a globular protein consisting only of amino acids. It is soluble in water, sparingly soluble in concentrated salt solutions and undergoes denaturation when exposed to excessive heat. It is the most abundant protein in human blood plasma. Its synthesis occurs in the liver (hepatocytes) and the speed of the process depends on the amount of proteins ingested (negative feedback regulation). It has a molecular weight of about 66KDa and a half-life between 15 and 19 days. The normal concentration of albumin in the blood varies between 3.5 and 5.0 g / dL. The catabolism of this protein takes place preferably in organs with high metabolic rates (liver, spleen and kidney). There are some types of albumins, whose name varies, depending on where they are most prevalent: serum albumin (present in blood plasma), ovalbumin (main protein from egg white), and lactalbumin (present in milk, is composed of high amounts of essential amino acids and, therefore has a high nutritional value). It is used in treatment of burns, hemorrhages and recovery operations, being also useful to reduce edema. It is essential for maintaining the osmotic pressure of blood (it accounts for 75-80% of the osmotic effect of plasma). Albumin has the function of transport and storage of various usually poorly soluble compounds in water with low molecular weight. For example, albumin is essential for the transport of unconjugated bilirubin to the liver and long chain fatty acids to extrahepatic tissues, and also the thyroid hormones, fat-soluble hormones and calcium ions. This protein is also responsible for the control of blood pH and blood viscosity. It also has an important role in lipid metabolism. Deficiencies in this protein concentration can trigger conditions such as hyperalbuminemia (excess albumin in the blood) and hypoalbuminemia (albumin deficit in blood). In the first case, the symptoms are most pronounced in conditions of severe dehydration, being a rare condition with a neglected diagnosis in most cases. Hypoalbuminemia results from reduction of protein synthesis, which may be caused by liver diseases (causing decreased protein production), malnutrition, malabsorption (due to, e.g., intestinal disorders), infections, excessive excretion thereof and in rare cases, genetic disorders. If the concentration of the protein decreases, the osmotic pressure of the blood decreases. Consequently, the plasma tends to seep into the intercellular spaces, causing edema, hence that administration of albumin after surgery is responsible for the reduction of swelling.

Text written by:

Mariana Rebelo

Marta Duarte

Rafael Honório

Sara Silva

.

Cartoon - Pepetide bond

Isoelectric point (aminoacids and proteins)

Amino acids are, as mentioned in other posts, molecules that have an amino group and a carboxylic group. These two groups are ionizable, ie, they may undergo protonation/deprotonation. Moreover, the side chains of various amino acids may present additional ionizable groups. This means that amino acids are molecules that can display positive, negative, or neutral charge. What influences the overall charge of each amino acid in a given context is:
1. Chemical composition of the amino acid and the molecule where it is inserted (if that is the case ...). The presence of certain atoms/functional groups in a molecule alters the distribution of its electron cloud, making some covalent bonds stronger and other weaker. The weakening of the bonds involving hydrogen atoms turn easier the occurrence of deprotonation.
2. The pH of the solution in which the amino acid is inserted. As is logical, functional groups will present a state of protonation that is influenced by the pH, that means, if the pH is lower than its pKa, the functional group tends to be protonated, and if it is greater than the pKa, it tends to be deprotonated.
Therefore, based on the characteristics of each amino acid, and the environment where it is, it is possible to obtain different total charges.
The isoelectric point is defined as the pH value for which the total charge of the amino acid is zero. Note that this does not mean that there are no charges on the amino acid, because in reality there are charges, indeed. This means is that when subjected to this pH, total positive charges equal the total negative charges. At this point, the amino acid solubility decreases. When an amino acid is placed in a solution with a pH below its isoelectric point, it acquires positive charge as the functional groups tend to be protonated (gain H+). If the pH is above the isoelectric point, total charge is negative, because the functional groups tend to be predominantly deprotonated (lose H+).

In the case of proteins, it applies exactly the same concept. However, in this case one must consider the total of ionizable groups present in the molecule, and the isoelectric point is defined as the pH value for which the total charge of the protein is zero. 

Again, at this value the solubility of the protein is zero, and it tends to precipitate. This is explored in the laboratory by means of a technique called isoelectric focusing.

.

Vasopressin

Vasopressin (væsoʊprɛsən / vaso + -in + pressure), also known as antidiuretic hormone (ADH) has a molecular weight of 1228 kDa and is formed by the following sequence of nine amino acids: cysteine ​​- tyrosine - phenylalanine - glutamate - aspartate - cysteine ​​- proline - arginine - glycine. The presence of a disulfide bridge between the cysteines in position 1 and 6, gives it a ring-shaped structure. In most species, the 8th position of the molecule is occupied by arginine and due to that, ADH is therefore also called arginine vasopressin or argipressin (AVP). Lysine vasopressin has a lysine in the traditional arginine position. In 1955, Du Vigneaud won the Nobel Prize in Chemistry, in part, by the discovery of vasopressin and oxytocin, a hormone related to vasopressin. In kidney, vasopressin increases the permeability of the renal tubule cells to water. As a result, it allows the body to retain water, increasing urine concentration and decreasing its volume. For this reason it is called antidiuretic hormone (ADH). 

Also, it promotes arteriolar vasoconstriction, increasing consequently the peripheral resistance and blood pressure. For this reason it is also called vasopressin. It also has other functions such as regulation of circadian rhythms, homeostasis and different social behaviors.This hormone is produced by the neurohypophysis, but can also be produced by the hypothalamus at the supraoptic and paraventricular levels of the core. The production of vasopressin begins with the activation of the gene responsible for its biosynthesis. This gene is located on chromosome 20 and has 3 exons separated by 2 introns. Each exon codes for one of the three domains of the precursor molecule of vasopressin.
Under enzymatic action, this precursor loses the signal peptide and is stored in vesicles at the Golgi complex, and then is transported from the cell body of the neuron to the nerve endings. This transport takes approximately 12 to 24 hours. During this time, several cleavages occur, giving rise to ADH molecules, neurophysin and copeptin. ADH is excreted by the neurohypophysis briefly in response to decreases in plasma volume (detected by barorrecetores), potential increases in osmotic plasma (detected by osmorecetores veins, arteries, and other vessels) and also in response to cholecystokinin (excreted by small intestine).
The diseases associated with vasopressin normally give a deficiency or excess in its production or in its effect. Disability can cause polyuria, excessive excreted urine which is hypotonic and when combined with hypernatremia (excess sodium in the blood) may be a sign of diabetes insipidus. The term diabetes refers to water loss, which is insipidus due to the absence of sweetnessin the urine. Diabetes insipidus arises from the lack of production of the hormone ADH. The excess of ADH is characterized by fluid retention and can lead to hyponatremia. It often happens in drops in blood pressure, reduced blood volume (amount of circulating blood) or dehydration. The excess of ADH also occurs by inadequate secretion of vasopressin syndrome, caused by disorders in the central nervous system, cancer, lung disease, and HIV medications and not by pressure drops and any of the other factors.

Text written by:
Luís Alves
Pedro Silva
Ricardo Praia
Tiago Fernandes
Tiago Borges
.

Amino acids with uncharged polar side chains

This class of amino acids includes those that do not have ionizable functional groups on its side chain. In fact, despite the definition of this class is given in this way, it is not 100% correct, because according to it, the aromatic amino acids should be included. Therefore, to be a completely correct definition, it must contain the word aliphatic, ie, amino acids that have an aliphatic side chain containing only non-ionizable functional groups. These amino acids can therefore establish non-covalent forces between their polar side chains. In particular, most of them can establish hydrogen bonds, a very important factor for the stability of the conformation of most proteins.

Several amino acids belong to this category:

Serine - This amino acid side has a small side chain with a hydroxyl group, which confers polarity. Under normal conditions the hydroxyl group is not ionized, although in some contexts (particularly on tyrosine, which is an aromatic amino acid such as highlighted in this post), it may function as a weak acid. All amino acids which have hydroxyl groups in the side chain are potential phosphorylation sites, which means, when a protein is phosphorylated, the phosphate groups are usually added to the hydroxyl groups of side chains.

Threonine - This amino acid, such as serine, has a hydroxyl group in its side chain, but in this case this chain is longer than that of serine.

Cysteine ​​- This amino acid deserves special attention because it is the only one of the 20 standard amino acids that has a sulphydryl or thiol group (more information about this functional group here). In addition to providing polarity, this functional group allows the establishment of disulfide bridges, which are the main type of covalent inter- and intramolecular bonds that contribute to the stability of the 3D structure of a protein. In a future post I will talk about the structure of proteins and the interactions that contribute to its stability.

 Proline - Other "special" amino acid! It is the only one of the 20 standard amino acids wherein the R group is covalently linked to the a-amino group, thus, the side chain forms a cyclic structure with the amino acid skeleton itself. The inclusion of this amino acid in the group of amino acids with uncharged polar aliphatic side chains is debatable, as there are those who put it in the group of amino acids with nonpolar aliphatic side chains. If we look closely, the side chain of proline is formed only by carbon and hydrogen, i.e., it is non-polar. However, as it is covalently bound to the nitrogen of the a-amino group, this will impart polarity to that structure. So, in my opinion, any one of the classifications may be used, it depends on the perspective. J Returning to proline cyclic structure, since it comprises the amino acid skeleton, it makes this amino acid more rigid than the remaining amino acids, as its side chain cannot freely rotate. Furthermore, the cyclic structure distorts the amino acid structure. As I always say in my classes, proline "is a wry amino acid", and this has significant implications for the effect of proline in the 3D structure of proteins.

Asparagine - This amino acid has in its side chain an amide group. In fact, in terms of composition, it is very similar to the aspartate amino acid, changing only the terminal functional group. By the way... a call to attention! The amide group is not an ionizable group, i.e., it does not confer basic (not acid!) properties to biomolecules. The basic functional group is the amino group.

 

Glutamine - As asparagine, glutamine also has an amide group in the side chain. In this case, there are obvious similarities with glutamate, although there is still a notorious difference, which is the amide group.