Desmosine is a proteinogenic amino acid. Together with other amino acids, it forms the fiber and structural protein elastin. In mutations in the ELN gene, the structural formation of elastin is impaired.
What is desmosine?
Amino acids are an important component of the human organism. They are a class of organic compounds formed from at least one carboxy group and one amino group. Thus, amino acids are both carboxylic acids and amines. Depending on their position in relation to the carboxy group, amino acids can be assigned to different groups. Amino acids with a terminal carboxy group are called geminal or α-terminal and belong to the α-amino acids. These amino acids are elements of proteins. The human body has more than 20 proteinogenic amino acids and 400 non-proteinogenic amino acids. The D-amino acids are a special group. One of the more than 20 proteinogenic amino acids is desmosine, which, together with isodesmosines of similar structure, forms the fibrous protein elastin. Elastin and its soluble precursor tropoelastin belong to the structural proteins and contribute to the shaping and support of anatomical structures. Elastin plays a special role in the stretching ability of large blood vessels, such as the aorta.
Function, effect, and tasks
Desmosine is formally a quadruple amino acid. It bears a pyridinium ring in its center. Pyridine is the name given to a chemical compound with the molecular formula C5H5N, which belongs to the heterocyclic parent systems and forms the simplest azine in the form of a six-membered ring with one nitrogen atom and five carbon atoms. Its central pyridinium ring enables desmosine to crosslink the individual protein strands in the fiber protein elastin. The composition of elastin is similar to collagen. Instead of hydroxylysine, however, elastin has a significant proportion of valine. Lysine residues are oxidized into allysine by the enzyme lysyl oxidase. Three allysines and one lysine in turn form a desmosine in ring form. This form plays a considerable role in the elasticity of an overall molecule of elastin. As a protein network, elastin consists of desmosine cross-linked units and is elastically stretchable. The lungs, skin and blood vessels all depend on elastin and its component desmosin, as this is what gives them their considerable elasticity. Desmosine fluoresces blue under UV light and gives elastin its yellow color, water insolubility, heat stability and resistance to alkalis and proteases.
Formation, occurrence, properties, and optimal values
The formation of desmosine is also known as desmosine biosynthesis. In this biosynthesis, the terminal amino groups of L-lysine units are converted to ω-aldehydes by oxidation by the enzyme lysyl oxidase. Lysyl oxidase is a protein lysine-6-oxidase and thus corresponds to an enzyme found in the extracellular space of connective tissue. In the cross-linking of elastin and collagen, it serves as a catalyst and mechanical stabilizer of proteins. In the biosynthesis of desmosine, lysyl oxidase converts lysine to allysine. This process takes place in the extracellular matrix and stabilizes the cross-links of collagen and elastin.Chemically, the reaction corresponds to oxidative deamination to aldehyde. Allysine forms either allysinaldol or desmosine with aldehyde residues of neighboring tropelastin molecules by an aldol condensation. Remaining lysine forms a Schiff base via its amino group and gives rise to isodesmosine. In addition to the blood vessels, the lungs and the skin, all microfibrils in particular carry desmosine. These are the smallest fibers of collagenous, reticular and elastic tissues.
Diseases and disorders
In various diseases, the formation of elastin from components such as desmosin is impaired. These disorders primarily include mutations in the ELN gene. The most important of these are dermatochalasis, Williams-Beuren syndrome, and subvalvular congenital aortic stenosis. Dermatochalasis is a group of connective tissue disorders with familial clustering. This group is characterized by sagging, poorly elastic, and wrinkled skin of various parts of the body. The ELN gene codes for elastin and can cause such manifestations through a mutation. Williams-Beuren syndrome is rare in comparison and affects only one in 20,000 newborns. A defect on chromosome seven underlies the disease.The gene locus is 7q11.23. Due to a defect at this site, the affected person lacks the elastin gene and adjacent genes. Deletion of the elastin gene causes facial dysmorphia and disorders of internal organ structure. Heart defects such as supravalvular aortic stenosis and kidney malformations such as horseshoe kidney or renal vascular stenosis may result. In addition, cognitive disability is often present. The mental abilities of the affected persons are below average. Despite verbal expressiveness, they form mostly content-poor sentences. They start reading at an extremely early age, which often overestimates their mental abilities. In addition to their hyperlexia, their often absolute hearing also frequently leads to overestimation. Subvalvular congenital aortic stenosis, as a form of elastin mutation, again corresponds to a heart malformation associated with narrowing of the great aorta. Supravalvular stenosis is located above the aortic valve at the beginning of the aorta. This form of heart defect is often characterized by hourglass-shaped narrowing that lies over the outlet of the coronary arteries. The ascending portion of the aorta may also be narrowed. This form of aortic stenosis is particularly common in the context of Williams-Beuren syndrome, just discussed. This heart defect has also been observed independently of the disease. In this case, however, it does not necessarily have to be related to a mutation of the elastin gene.
