Lysyl oxidase is an enzyme of connective tissue that has catalytic functions and promotes the cross-linking of collagen and elastin. The enzyme has a stabilizing effect on connective tissue by performing oxidative deamination, thereby creating the basic conditions for cross-linking. In cutis laxa, the activity of lysyl oxidase is decreased.
What is lysyl oxidase?
There are different enzymes in the human body, all of which have catalytic activity. So, enzymes enable or accelerate reactions in the human body. Lysyl oxidase is an enzyme of the human connective tissue. It is also called protein lysine-6-oxidase and is found mainly in the extracellular space of connective tissue. In this case, the catalytic activity of the enzyme relates to the cross-linking between collagen and elastin. Lysyl oxidase mechanically stabilizes the two proteins, thus enabling the reactive bond. Lysyl oxidase is not only found in the human body. Other vertebrates are also equipped with the enzyme. Lysyl oxidase is considered a stabilizer of connective tissue. A deficiency of the enzyme causes the clinical picture of cutis laxa, a severe and hereditary connective tissue weakness.
Function, effect, and tasks
Lysyl oxidase performs important functions in the extracellular space in the cross-linking between individual molecules of collagen. In the human body, collagen has a major role within proteins, accounting for approximately 30 percent of total protein mass. Collagen is the most abundant protein. It is a structural and building protein that makes up many components of the body, including connective tissue, bones, teeth, cartilage, tendons, ligaments and skin. Lysyl oxidase supports the binding of collagen to carbonyl groups and thus contributes its part to the stability of the aforementioned body components. It has catalytic activity for the production of carbonyl groups that form covalent cross-links on collagens in aldol condensations. Accordingly, the catalytic task of lysyl oxidase is the preparation of fibril formation. The enzyme creates all the chemical conditions necessary for formation. Fibrils are considered to be fibers of fiber. They correspond to thin and fibrous body components and are found in plant cell walls, in human muscles and in connective tissue. The task of lysyl oxidase in this context is essentially the oxidative deamination of lysyl residues. In chemistry, deamination is the chemical cleavage of amino groups as ammonium ions or ammonia. Oxidative deamination cleaves amino groups of the amino acid L-glutamate from hydrogen and oxidizes them to imino groups with the transfer of hydrogen to NAD+ or NADP+. This is followed by hydrolytic cleavage of imino groups as ammonium ions, which is accompanied by the formation of α-keto acid. Deamination corresponds to the first step in the biochemical degradation of amino acids, which in mammals occurs mainly in the liver. The ammonium ion formed during deamination is converted to urea. The deamination processes of lysyl oxidase give rise to aldehyde groups, which can combine with the individual amino groups from other lysyl residues to form so-called Schiff bases and in this way form the stabilizing cross-links in collagen.
Formation, occurrence, properties, and optimal values
Lysyl oxidase is encoded in DNA by the LOX gene, which in humans is located on chromosome 5 in gene locus q23.3 to q31.2. The gene product is not the final form of the enzyme. The product is not finished lysyl oxidase, but a precursor form that has a molar mass of 47 kDa after translation. Glycosylation occurs in the further course. During this process, the molar mass of the later enzyme increases to 50 kDa and the precursor form of lysyl oxidase is secreted into the extracellular space. After secretion, the pre-pro lysyl oxidase is further processed. In the extracellular space, the substance is cleaved. The cleavage into two fragments is carried out by protein 1, resulting in the 32 kDa lysyl oxidase. On the other hand, a residual substance is formed, which in this case corresponds to a polypeptide.
Diseases and disorders
Genetic defects of lysyl oxidase can cause the clinical picture of cutix laxe.This condition is also called dermatochalasis and refers to a group of often age-related connective tissue weaknesses observed in most cases with familial clustering. The common characteristic of all dermatochalasis phenomena is sagging and inelastic skin that often hangs down in large folds on various parts of the body. Most affected individuals look older than they are because of the changes. The disorders are caused, among other things, by genetic mutations. In this context, there is talk of cutis laxa syndrome. The disease can be in autosomal recessive, autosomal dominant and x-chromsomal form. In many cases, cutis laxa syndrome is associated with other abnormalities and can be fatal if organs are involved, for example. ARCL1 corresponds to cutis laxa of autosomal recessive type 1 and is considered the most severe form, which may cause life-threatening complications. Type ARCL1A is associated with mutations in the FBLN5 gene at locus 14q32.12. Type ARCL1B is associated with mutations in the EFEMP2 gene at locus 11q13.1, and variant ARCL1C corresponds to cutis laxa with associated lung, gastrointestinal, and urinary tract abnormalities due to mutations in the LTBP4 gene at locus 19q13.2. The mutations in the aforementioned genes result in below-average activity of lyxyloxidase. The decreased activity of the enzyme creates insufficient cross-links. Thus, the patients’ connective tissue is not sufficiently stabilized.
