In the human body there is a huge setbiochemical reactions aimed at maintaining vital functions, such as energy production, growth and development, the relationship of individual organs and body systems, protection from infections. Among the vital functions have this - the splitting of large biomolecules into components and their withdrawal from the body. Failure of this function leads to disease mucopolysaccharidosis type, including Hunter syndrome. Splitting large biomolecules into small molecules occurs under the influence of special substances - enzymes. Enzymes are formed in the cells. Enzymes are necessarily present in all cells of a living organism. Accelerating biochemical reactions, enzymes direct and regulate metabolism. All living cells contain a very large set of enzymes, the activity of which depends on the functioning of cells. Almost each from a variety of reactions in the cell, it requires the participation of a specific enzyme. Enzymes that break down macromolecules are in special bags cell - lysosomes.
Biochemistry of Hunter syndrome is related to the problempart of the connective tissue, and it is the intercellular substance. The composition includes extracellular matrix fibers (collagen and elastic) and a basic substance which prevails in volume. The fibers are arranged disordered, form a loose network.
Intercellular substance is composed of a variety ofsugars and proteins and helps to shape the structure of an organ. Intercellular substance surrounds individual cells if the network and functions as the glue that holds the individual cells. One of the components of the intercellular substance have complex molecules called proteoglycans. Like many of the components of the human body, proteoglycans from time to time have to be destroyed and replaced with new ones. Upon cleavage of proteoglycans form mucopolysaccharides, otherwise called glikozaminklikanami (GAG).
The mechanisms occurring in the skin
To better understand what glycosaminoglycans, consider the mechanisms occurring in the skin. We all know that human skin consists of three layers - the epidermis, dermis and hypodermis.
The dermis acts as a framework which providesflexibility, strength and stretchability of the skin. The dermis can be easily compared to a sort of unusual mattress: spring water and at the same time. The mattress springs are playing the role of collagen and elastin fibers, the space between them is filled with an aqueous gel composed of mucopolysaccharides (glycosaminoglycans). Incidentally, the collagen molecules do resemble springs, as they are twisted thread protein-like helices.
The resiliency and stability of the dermis, where"Resting" the epidermis, is defined as the state of "springs" - collagen and elastin fibers, as well as the aqueous gel formed by glycosaminoglycans. If the "mattress" is not in order - weakened "spring", or gel does not hold moisture - the skin begins to sag under the force of gravity to shift and stretch while sleeping, laughing and crying, wrinkle and lose elasticity. It forms large folds, such as nasolabial.
In young skin collagen fibers andglycosaminoglycan gel is constantly updated. With age, the renewal of the intercellular substance of the dermis is slower to accumulate damaged fibers, glycosaminoglycans and the number is steadily decreasing.
The main objective of the dermis cells - to destroy andbuild (synthesize) the intercellular substance (glycosaminoglycans). Basically it involved cells - fibroblasts. Fibroblasts can be considered as the builders and architects of determining the composition and structure of the connective tissue of the skin. It is they who first destroy collagen and hyaluronic acid, and destroying, synthesize these molecules again. The process of destruction, recovery takes place continuously and constantly updated thanks to him, the intercellular substance.
In aging skin fibroblast activityreduced, and they are getting worse cope with their responsibilities. Particularly rapidly lost the ability to form the intercellular substance. But the destructive ability, unfortunately women have long been at the same level. As they say, break - not to build. In aging skin collagen fibers become thicker, but the number and elasticity decrease. As a result, the collagen matrix structure is broken, the moisture content in the intercellular substance of the derma decreases, and the skin, respectively, loses elasticity.
The role of the dermis and glycosaminoglycans
The dermis acts as a framework which providesMechanical properties of the skin - its elasticity, strength and elongation. It resembles a combination of water and a spring mattress, the springs where the role played by the fibers of collagen and elastin, the space between them is filled with an aqueous gel composed of mucopolysaccharides (glycosaminoglycans). Collagen molecules actually resemble springs, ie. k. a protein filaments are twisted like spirals. Glycosaminoglycans - a large molecules of carbohydrates, which do not dissolve in water and are converted to mesh, which cells capture large amounts of water - a viscous gel.
The epidermis - it is the top, constantly updatedlayer of the skin. With his associates dermis special structure - the basement membrane. It recalls mat woven of protein fibers and impregnated with a gel substance (glycosaminoglycans). Near the basement membrane of the dermis contains more glycosaminoglycans, and its "spring" softer. This so-called papillary dermis. It forms a soft cushion directly below the epidermis. Under the papillary layer is a mesh layer, where collagen and elastin fibers form a rigid support grid. This grid also impregnated glycosaminoglycans. Mainly dermis glycosaminoglycan is hyaluronic acid, which has the largest molecular weight and binds most water.
Condition dermis of the mattress on whichrests epidermis, its elasticity and resistance to mechanical stress is defined as the state of "springs" - collagen and elastin fibers, as well as the aqueous gel formed by glycosaminoglycans. If the mattress is not in order - weak springs or gel does not hold moisture - the skin begins to sag under the force of gravity to shift and stretch while sleeping, laughing and crying, wrinkle and lose elasticity. In young skin and collagen fibers and glycosaminoglycan gel is constantly updated. With age, the renewal of the intercellular substance of the dermis is slower to accumulate damaged fibers, glycosaminoglycans and the number is steadily decreasing.
Tissue distribution glycosaminoglycans
There are several types of glycosaminoglycans,each of which is formed in some specific places in the body. In turn, glycosaminoglycans must also be split into smaller components which the organism is able to bring the outside.
Glycosaminoglycans and their distribution in tissues
hyaluronic acid formed in the eye (vitreous), joints (synovial fluid), skin, cartilage, bone,
Chondroitin formed in the cornea, aorta, cartilage, skin, bone, sclera
Chondroitin-4-sulphate It formed in the cartilage, skin, tendons,
Chondroitin-6-sulphate It formed in the cartilage, skin, tendons,
heparin It formed in the skin, lung, liver, blood vessels
heparan sulfate formed in the lungs, aorta
I keratan formed in the cornea
keratan sulfate II formed in the cartilage
dermatan formed in the skin, tendon, sclera, cornea, heart valves
In Hunter syndrome, there is a problem whensplitting the two glikozaminklikanov - dermatan sulfate and heparan sulfate. The first step in the splitting of glikozaminklikanov requires particular lysosomal enzyme I2S (enzyme, located in a special pouch in the cell - the lysosome). In people with the same Hunter syndrome or the enzyme produced in insufficient quantities, or not produced at all. As a result glikozaminklikany deposited in cells throughout the body, especially in tissues that contain high amounts of heparan sulfate and dermatan sulfate. As a result of the accumulation of glikozaminklikanov internal organs and body systems begin to malfunction, resulting in numerous serious injury. Although the rate of accumulation glikozaminklikanov in people with Hunter syndrome is not the same, the result is all the same turns out a wide range of medical problems.