Hyaluronic acid is an animal product that 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 in the process of 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. For the first time, this high molecular weight compound was isolated from the vitreous of cattle. At first, scientists suggested that the substance is characteristic only of mammals. However, in 1937 this was disproved - it was obtained from a liquid medium in which hemolytic streptococcus was cultivated. In 1954, the structural formula of hyaluronic acid was first published in the British journal "Nature".
The commonly used name of a substance is associated with the history of its discovery (English โhyaloidโ - glassy, โโโuronic acidโ - uronic acid). In international chemical terminology, there is also the name "hyaluronan", which combines acid and its salts. The chemical formula of hyaluronic acid is: CโโHโโNโOโโ.
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 future use, so the demand for this biopolymer is constantly growing.
Structure
The 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 a variety of isomers - compounds that differ in the spatial arrangement of atoms. Their chemical properties also vary. Hyaluronic acid, unlike glucose aminoglycans, is always chemically identical. Its properties do not depend on the methods of preparation and 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 acid contains hydrophobic and hydrophilic sites, so this high-molecular-weight compound in space has the form of a twisted tape. 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 saturation of tissues with water and maintaining internal volume.
Chemical properties
Hyaluronic acid has the following characteristic chemical properties:
- the formation of a large number of hydrogen bonds;
- creating an acidic reaction of the medium in aqueous solutions due to the presence of a deprotonated carboxyl group;
- the formation of soluble salts with alkali metals;
- the 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.
Externally, aqueous solutions of the substance resemble egg white in consistency. The structural formula of hyaluronic acid allows it to take several forms, depending on the ionic environment of the medium:
- left single spiral;
- multi-strand flat structures;
- double helix;
- supercoiled structures with a dense molecular network.
The latter form is tertiary and is capable of absorbing a large volume of water, electrolytes, and high molecular weight proteins.
Differences in hyaluronic acid of various origins
As already mentioned above, the structure of this substance is very similar regardless of the source of its production. The difference between acids of bacterial and animal origin is the degree of polymerization. The formula of hyaluronic acid obtained from animal sources has a longer length compared to the bacterial form (4,000-6,000 and 10,000-15,000 monomers, respectively).
The solubility in water of these substances is the same and depends mainly on the presence of hydroxyl and salt groups in disaccharide residues. Since the chemical structure of the acid is inherently similar in all living individuals, this minimizes the risk of negative immunological reactions and rejection when it is introduced into the human and animal body.
Role in nature
The main location of hyaluronic acid is the composition of the intercellular (or extracellular) matrix of mammalian tissue. As scientific studies show, it is also found in the capsules of some bacteria - streptococci, staphylococci and other parasitic microorganisms. The synthesis of the compound also occurs in the body of invertebrates (protozoa, arthropods, echinoderms, and worms).
Scientists suggest that the ability to produce hyaluronic acid in bacteria formed evolutionarily to increase their virulent properties in the host. 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 membrane or membranes of intracellular organelles. The highest concentration of the substance in the human body is noted in the fluid filling the joint cavities, in the umbilical cord, vitreous body of the eye and 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.
- Aminosugar - 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 disintegrated per day in the human body. 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 protein-enzymes (hyaluronate synthetases). They are metalloproteins consisting of metal cations and glucoside phosphates. Hyaluronate synthetases are the only enzymes that catalyze acid production.
The process of destruction of CโโHโโNโOโโ molecules occurs under the influence of hyaluronatlytic enzymes. In the human body there are at least seven, and some of them suppress the processes of tumor formation. The decomposition 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 depend. CโโHโโNโOโโ performs the following functions:
- water conservation, which ensures the elasticity of the skin and its turgor;
- the creation of the necessary degree of viscosity of the intercellular fluid;
- participation in the reproduction of basic and immunocompetent epidermal cells;
- maintaining the growth and restoration of damaged skin;
- strengthening collagen fibers;
- strengthening local immunity;
- protection against free radicals, chemical and biological agents.
The highest concentration of this substance is observed in the skin of the embryo. During aging, most of the acid is bound by proteins, due to which the level of hydration of the skin decreases. The ability to self-regulate metabolism in people older than 50 years is especially reduced.
The following properties of hyaluronic acid in the composition of the synovial fluid were also determined:
- the formation of a homogeneous structure to retain a specific component of the cartilage tissue - chondroitin sulfate;
- strengthening the collagen frame of cartilage;
- providing lubrication of the 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 1,500 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 weight compounds have the most striking antioxidant properties.
Hyaluronic acid is also involved in the formation and development of the embryo, in the management of cell motility - the migration of cells from one place to another, in some interactions with surface cell receptors.
Getting
There are 2 main groups of methods for producing substances:
- Physico-chemical (extraction from the tissues of mammals, vertebrates and birds). Since the acid is often found in animal feed in combination with proteins and other polysaccharides, thorough purification of the resulting product is required, which affects the cost of the final product. To produce acid on an industrial scale, the umbilical cord of newborn children and the crests of domestic chickens are used. There are other extraction methods - from the eyes of cattle, fluid that fills the cavity of joints and joint bags; blood plasma, cartilage, pig skin.
- Microbial methods based on bacteria cultured in a nutrient medium. The main producers are the bacteria Pasteurellamultocida and Streptococcus. These methods were first tested in 1953. They are more economical and also not dependent on seasonal supplies of raw materials.
In the first case, biological materials are destroyed by grinding and homogenization methods, and then the 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 with amyl alcohol. After this, the substance is concentrated on activated carbon. Final purification is done by ion exchange chromatography or by cetylpyridinium chloride precipitation.
Use in medicine
Hyaluronic acid is used for the following pathologies:
- ophthalmology - cataract; use as a surgical environment during operations;
- orthopedics - osteoarthritis, protection of the articular cartilage from destruction, as well as to stimulate its recovery (endoprostheses of synovial fluid);
- surgery - an increase in the volume of soft tissues, operations with extensive excision of cartilage tissue;
- Pharmaceuticals - the manufacture of drugs based on the polymer structure of the compound (tablets, capsules, creams, gels, ointments);
- food industry - sports nutrition;
- gynecology - anti-adhesion drugs;
- Dermatology - treatment of burns, post-thrombotic trophic skin disorders.
According to 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 being conducted on the development of drugs and dietary supplements with anti-inflammatory and immunomodulatory effects, which can be used in many sectors of human activity.
Cosmetology
In cosmetology, this compound is used to correct age-related changes. Due to the fact that the acid structure is similar for all living organisms, it is suitable for use as a dermal filler (injection), especially around the eyes. In order for the substance to remain longer in the epidermis, it is modified using crosslinking molecules (crosslinkers). โCrosslinkedโ fillers differ from each other in 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.
CโโHโโNโOโโ is also added to the composition of external cosmetics - gels, foams, creams and other basic products. Hyaluronic acid in the composition is designated as hyaluronic acid (and sodium hyaluronate - sodium hyaluronate). This type of cosmetic product has the same properties as fillers - it prevents the formation of wrinkles, blackheads, and helps to saturate the skin with moisture.