Metabolic map about the metabolism of vitamin C in central nervous system

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
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Standard and non-standard amino acids

Amino acids are molecules that, from a chemical standpoint, are characterized by the presence of an amine group and a carboxylic group (acid), and hence its name: amino acid. Its main function is to serve as monomers for the synthesis of peptides and proteins. Of all the amino acids in nature, there is a set of 20 amino acids which are designated by standard amino acids, and that are used as building blocks for most of the proteins produced by any living being. These amino acids are widely studied and have been the central elements in my last posts. Just to remember, the standard amino acids are:

- glycine
- alanine
- proline
- valine
- leucine
- isoleucine
- methionine
- phenylalanine
- tyrosine
- tryptophan
- serine
- threonine
- cysteine
- asparagine
- glutamine
- lysine
- arginine
- histidine
- aspartate
- glutamate

However, besides the standard amino acids, there are many others that are found in some proteins and are called non-standard amino acids. The idea of ​​using these non-standard amino acids is simple to understand. By having a composition different from the standard amino acids, they present different physicochemical properties. Therefore, when it is necessary to introduce in a protein a local with certain properties, if they cannot be provided by the standard amino acid, it is incorporated in the sequence a non-standard amino acid. With regard to translation, in these cases, at these sites are introduced standard amino acids, which suffer post-translation covalent modifications to give amino acids with other features. I would like to highlight something that I think it is important. How you will notice below, several of the non-standard amino acids are found in the extracellular matrix proteins. As the extracellular matrix is a very complex structure, establishing numerous interactions with many different molecules (extracellular and cellular molecules), it is necessary that the proteins that make up the matrix may present a high versatility in the interactions that they establish, hence the need to specifically include some amino acids that have different characteristics. Some non-standard amino acid examples include:
- Cystine, desmosine and isodesmosine, which are amino acids found in extracellular matrix proteins such as elastin;

 

- Hydroxyproline and hydroxylysine, found in the most abundant protein of  the extracellular matrix – collagen;

 

- Gamma-carboxyglutamate, found in osteocalcin which is an extracellular matrix protein of bone, but also in the pro-thrombin, which is important for the coagulation cascade;

- Phosphoserine, phosphothreonine and phosphotyrosine, which are found in many different proteins, as protein phosphorylation is the most common post-translational modification, and always involves amino acids with hydroxyl groups in their side chains;

- N-acetillysine, which is fundamental to the structure of histones:

- Methyllyisine, which is found in myosin, a motor protein of our cytoskeleton, more specifically of actin filaments.

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Amino acids with acidic side chains

This is the latest group of standard amino group that I will describe. It consists of 2 amino acids, glutamate (also called glutamic acid) and aspartate (also called aspartic acid). Both have a carboxylic group in its side chain, which, being a weak acid group, confers acidic properties to the side chain. In other words, these side chains tend to have a negative charge as a result of deprotonation of the carboxylic group. They are, therefore, very important amino acids to establish ionic interactions with amino acids with alkaline side chains (more information on these amino acids here), and these forces may also be called salt bridges. In order to avoid confusion in the nomenclature of the carboxylic group of the side chain and the carboxylic group attached to the alpha carbon, the side chain group is typically referred to as gamma-carboxylic. The difference between glutamate and aspartate is just a methylene group -CH2 -. Indeed, glutamate has one more carbon (in the form of methylene group) than aspartate. Both can be obtained from intermediates of the Krebs cycle (glutamate from alpha-ketoglutarate and aspartate from oxaloacetate), and besides being building blocks for protein synthesis, they are also used as neurotransmitters. Glutamate also plays a very important role in terms of the sense of taste, and is also important as a donor of amino groups in several reactions of biosynthesis of nitrogenous molecules.

Amino acid with alkaline side chains

This class of amino acids includes those amino acids who have in their side chain an alkaline functional group. This means that these amino acids tend to have positive charge on their side chain as the alkali groups tend to pick up H+. As a result, they usually establish ionic bonds (or salt bridges) with amino acids with negatively charged side chains There are 3 amino acids belonging to this class:

Lysine - This amino acid has in its side chain a primary amine, that means, an amine group which is bonded to only one carbon, while the remaining nitrogen substituents are hydrogen atoms. The amine group is the main alkaline group in biochemistry (more information on this post). Lysine is the primary site of glycosylation of proteins, and in this case, the established connections are N-glycosidic bonds.

 

Arginine - This amino acid has in its side chain a more complex alkali functional group, called guanidine. This is a functional group comprising 3 nitrogen atoms, which displays electronic resonance, and they can be protonated.

Histidine - This amino acid has a cyclic structure in its side chain, more specifically an imidazole ring. It is a heterocycle composed of nitrogen and carbon atoms, in which one of the nitrogens can be protonated. Histidine has a particularly important feature in biochemistry: it is the only amino acid that has substantial buffering capacity at physiological pH (between 6.5 and 7.5), since its pKa is about 6. In this regard, it should be noted, firstly, that the pKa of histidine changes, as this amino acid is inserted into different polypeptide chains, but usually it is not much different from the original value (isolated histidine). Also, the fact that it is important to have a pKa close to physiological pH, relates to the ability of histidine to exist in medium in its acid and alkaline forms at the physiological pH, functioning as an acid-base pair conjugate.

Cartoon - Insulina's mechanism of action