Hyaluronic acid is a product of animal origin, which is widely used in medicine and cosmetology. The properties of this substance are not yet fully understood, and its effect on the human body is promising for the creation of new generation drugs. This compound is actively involved in the processes of embryogenesis, cell division, their differentiation and movement during the immune response.
Discovery history and terminology
Hyaluronic acid according to the formula refers to glycosaminoglycans, the molecules of which consist of repeating units that do not contain sulfate groups. This high molecular weight compound was first isolated from the vitreous body of cattle. At first, scientists assumed that the substance was characteristic only of mammals. However, in 1937 this was refuted - it was obtained from a liquid medium in which hemolytic streptococcus was cultivated. In 1954, in the British general scientific journal Nature, it was first publishedstructural formula of hyaluronic acid.
The common name of the substance is associated with the history of its discovery (eng. "hyaloid" - vitreous, "uronic acid" - uronic acid). In international chemical terminology, there is also the name "hyaluronan", which combines the acid and its s alts. The chemical formula of hyaluronic acid is: C₂₈H₄₄N₂O₂₃.
Currently, the range of its application is very wide: medicine, cosmetology, pharmacy. Hyaluronic acid is used as the main and auxiliary substance. The properties of the compound, discovered in recent years, have great prospects for use in the future, so the demand for this biopolymer is constantly growing.
Building
Hyaluronic acid formula is a typical anionic polysaccharide. Molecules are connected in long linear chains. Related substances - glucose aminoglycans - have a large number of sulfated groups. This explains the formation of various isomers - compounds that differ in the spatial arrangement of atoms. Their chemical properties also differ. Hyaluronic acid, unlike glycosaminoglycans, is always chemically identical. Its properties do not depend on the methods of obtaining and the type of source materials.
The composition of hyaluronic acid includes D-glucuronic acid and N-acetyl-D-glycosamine, which are interconnected by a beta-glycosidic bond and form its disaccharide units (glucopyranose rings having a molecular weight of about 450 Da). Their number in the molecules of this compound can reach 25,000. Due to this, the acid has a high molecular weight (5,000-20,000,000 Da).
The structural formula of the disaccharide fragment of hyaluronic acid is shown in the figure below.
The composition of the acid contains hydrophobic and hydrophilic areas, due to which this high-molecular compound in space looks like a twisted ribbon. The combination of several chains form a ball of loose structure. The ability to bind and hold up to 1000 water molecules is another feature of the hyaluronic acid formula. The biochemistry of this substance is primarily due to its high hygroscopicity, which ensures the saturation of tissues with water and the maintenance of internal volume.
Chemical properties
Hyaluronic acid has the following characteristic chemical properties:
- formation of a large number of hydrogen bonds;
- creation of an acid reaction of the medium in aqueous solutions due to the presence of a deprotonated carboxyl group;
- formation of soluble s alts with alkali metals;
- formation in an aqueous solution of a strong gel structure (pseudogel) containing a significant amount of moisture (protein complexes often precipitate);
- creation of insoluble complexes with heavy metals and dyes.
Outwardly, aqueous solutions of a substance resemble egg white in consistency. The structural formula of hyaluronic acid allows you to takeit has several forms, depending on the ionic environment of the medium:
- left single helix;
- multifilament flat structures;
- double helix;
- supercoiled structures with a dense molecular network.
The last form is tertiary and is able to absorb a large amount of water, electrolytes, high molecular weight proteins.
Differences in hyaluronic acid of various origins
As mentioned above, the structure of this substance is very similar, regardless of the source of its receipt. The difference between acids of bacterial and animal origin is the degree of their polymerization. The hyaluronic acid formula derived from animal sources is longer than the bacterial form (4,000-6,000 and 10,000-15,000 monomers, respectively).
The solubility in water for these substances is the same and depends mainly on the presence of hydroxyl and s alt groups in disaccharide residues. Since the chemical structure of the acid is inherently similar in all living individuals, this minimizes the risk of adverse immunological reactions and rejection when administered to humans and animals.
Role in nature
The main location of hyaluronic acid is the composition of the intercellular (or extracellular) matrix of mammalian tissues. As scientific studies show, it is also present in the capsules of some bacteria - streptococci, staphylococci and other parasitic microorganisms. The synthesis of the compound also occurs in the body of invertebrate animals (protozoa,arthropods, echinoderms, worms).
Scientists suggest that the ability to produce hyaluronic acid in bacteria has evolved to increase their virulent properties in the host organism. Due to its presence, microorganisms can easily penetrate the skin and colonize it. Such parasitic bacteria are able to neutralize the host's immune response and provoke the development of a more active inflammatory process than other strains of microbes.
Hyaluronic acid is produced by proteins that are embedded in the cell wall or membranes of intracellular organelles. The highest concentration of a substance in the human body is noted in the fluid that fills the cavities of the joints, in the umbilical cord, the vitreous body of the eye and the skin.
Metabolism
The synthesis of hyaluronic acid takes place in the form of enzymatic reactions in 3 stages:
- Glucose-6-phosphate – glucose-1-phosphate (phosphorylated glucose) – UDP-glucose – glucuronic acid.
- Amino sugar – glucosamine-6-phosphate – N-acetylglucosamine-1-phosphate – UDP-N-acetylglucosamine-1-phosphate.
- Glycoside transferase reaction involving the enzyme hyaluronate synthetase.
About 5 g of this substance is produced and broken down in the human body per day. The total amount of acid is about seven thousandths of a percent by weight. In vertebrates, acid synthesis occurs under the influence of 3 types of enzyme proteins (hyaluronate synthetases). They are metalloproteins composed of metal cations and glucoside phosphates. Hyaluronate synthetases are the only enzymescatalyzing the production of acid.
The process of destruction of C₂₈H₄₄N₂O₂₃ molecules occurs under the action of hyaluronan-lytic enzymes. In the human body, there are at least seven of them, and some of them suppress the processes of tumor formation. The breakdown products of hyaluronic acid are oligo- and polysaccharides, which stimulate the formation of new blood vessels.
Functions in the human body
Collagen and hyaluronic acid in the composition of human skin are the most valuable substances on which the elasticity and smoothness of the dermis depends. C₂₈H₄₄N₂O₂₃ performs the following functions:
- preservation of water, which ensures the elasticity of the skin and its turgor;
- creating the required degree of viscosity of the interstitial fluid;
- participation in the reproduction of the main and immunocompetent cells of the epidermis;
- support growth and repair of damaged skin;
- strengthening collagen fibers;
- strengthening local immunity;
- protection against the effects of free radicals, chemical and biological agents.
The highest concentration of this substance is observed in the skin of the embryo. With aging, most of the acid binds to proteins, which reduces the level of hydration of the skin. The ability to self-regulate metabolism is especially strongly reduced in people over 50.
The following properties of hyaluronic acid in synovial fluid have also been determined:
- formationhomogeneous structure to hold a specific component of cartilage - chondroitin sulfate;
- strengthening the collagen framework of the cartilage;
- providing lubrication of moving parts of the joints, reducing their wear.
The biological role of acid molecules differs depending on their molecular weight. Thus, compounds containing up to 1500 monomers have an anti-inflammatory effect and take an active part in the construction of the collagen network. Polymers with a chain of up to 2000 monomers play a role in maintaining hydrobalance, and high-molecular compounds have the most pronounced antioxidant properties.
Hyaluronic acid is also involved in the formation and development of the embryo, in the control of cell mobility - cell migration from one place to another, in some interactions with surface cell receptors.
Receive
There are 2 main groups of ways to obtain a substance:
- Physico-chemical (extraction from tissues of mammals, vertebrates and birds). Since acid is often found in animal raw materials in combination with proteins and other polysaccharides, a thorough purification of the resulting product is required, which affects the cost of the final drug. To obtain acid on an industrial scale, the umbilical cord of newborns and the combs of domestic chickens are used. There are other methods of extraction - from the eyes of cattle, the fluid that fills the cavities of the joints and articular bags; blood plasma,cartilage, pigskin.
- Microbial methods based on cultured bacteria. The main producers are the bacteria Pasteurellamultocida and Streptococcus. These methods were first tested in 1953. They are more economical and also do not depend on seasonal supplies of raw materials.
In the first case, biological materials are destroyed by grinding and homogenization methods, and then acid is extracted in a mixture with peptides by exposure to organic solvents. The resulting mass is treated with enzymes or proteins are removed by denaturation with chloroform or a mixture of ethanol and amyl alcohol. After that, the substance is concentrated on activated carbon. Final purification is done by ion exchange chromatography or precipitation with cetylpyridinium chloride.
Medical use
Hyaluronic acid is used for the following pathologies:
- ophthalmology – cataract; use as a surgical environment during operations;
- orthopedics - osteoarthritis, protection of articular cartilage from destruction, as well as to stimulate its recovery (synovial fluid endoprostheses);
- surgery - soft tissue augmentation, operations with extensive cartilage excision;
- pharmaceuticals - production of drugs based on the polymer structure of the compound (tablets, capsules, creams, gels, ointments);
- food industry - sports nutrition;
- gynecology - antiadhesionfunds;
- dermatology - treatment of burns, post-thrombotic trophic skin disorders.
According to the forecasts of scientists, this substance can become the basis for a new group of drugs for the treatment of cancer.
Other properties of the acid are also promising:
- antimicrobial, antiviral effect (the compound is active against the herpes virus and others);
- improvement of blood microcirculation;
- anti-inflammatory effect;
- prolonged action (gradual dissolution in human tissues).
Vitamins
Hyaluronic acid as part of vitamins is used in the form of purified sodium hyaluronate, which is its analogue. The main purpose of the substance is to preserve the youthfulness of the skin, moisturize it, and heal wounds. To improve absorption, ascorbic acid is introduced into the composition of vitamin complexes.
Research is also underway to develop drugs and dietary supplements with anti-inflammatory and immunomodulatory effects that can be used in many areas of human activity.
Cosmetology
In cosmetology, this compound is used to correct age-related changes. Due to the fact that the structure of the acid is similar in all living organisms, it is suitable for use as a dermal filler (injection), especially around the eyes. In order for the substance to remain in the epidermis longer, it is modified with the help of cross-link molecules.(crosslinkers). Cross-linked fillers differ from each other in terms of gel viscosity, acid concentration, and duration of resorption in the skin.
Injections are administered intra- or subcutaneously in the form of a 1-3% aqueous solution. This helps to increase the elasticity and firmness of tissues, a noticeable smoothing of wrinkles.
C₂₈H₄₄N₂O₂₃ is also added to the composition of external cosmetics - gels, foams, creams and other basic products. Hyaluronic acid in the composition is referred to as hyaluronic acid (and sodium hyaluronate is sodium hyaluronate). This type of cosmetic product has the same properties as fillers - it prevents the formation of wrinkles, acne, and helps to saturate the skin with moisture.
