Glucosamine, a health food raw material that is conducive to improving the function of bones and joints

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Glucosamine (abbreviated as GlcN) is a natural amino monosaccharide, which is necessary for the synthesis of proteoglycans in the matrix of human articular cartilage.
Its molecular formula is C6H13NO5 and its molecular weight is 179.
2.
It is formed by the substitution of a hydroxyl group of glucose by an amino group, and is easily soluble in water and hydrophilic solvents.
Usually in the form of N-acetyl derivatives (such as chitin) or in the form of N-sulfate and N-acetyl-3-O-lactic acid ether (teichoic acid) in microorganisms, animal-derived polysaccharides and bound polysaccharides.

 

　　2.
The source of glucosamine

 

　　Glucosamine is widely present in the cell walls of fungi and the exoskeleton of shrimps and crabs, and is a component of chitin and chitosan.
In nature, GlcN is also widely present in bacteria, yeast, fungi, plants and animals.
GlcN is also the main component of glycoprotein and proteoglycan.
It is abundantly present in the articular cartilage tissue and eye lens of humans and animals.
It is an important nutrient for the formation of cartilage cells; it is a natural component of glycoprotein in the joint tissues of humans and animals.
Endogenous biosynthesis by glucosamination in animals and humans.

 

　　Three, the function of glucosamine

 

　　Glucosamine has a variety of functions and is widely used in food, medicine, and cosmetics.
After searching on the special food information query platform of the General Administration of Markets, there are 261 health food document numbers containing glucosamine in the formula, and 80% of the functions are claimed to be Increase bone density, as well as improve immunity, anti-oxidation and other functions.

 

　　1.
Immune regulation.
Glucosamine participates in carbohydrate metabolism in the body and is widely present in the body.
It can participate in the construction of human tissues and cell membranes.
It is an intermediate substance in the synthesis of proteoglycan macromolecules.
It can synthesize mucopolysaccharides, glycoproteins and proteoglycans.
It can be combined with other substances such as galactose.
, Glucuronic acid and other substances combine to form important products with biological activity such as hyaluronic acid and keratin sulfuric acid, which participate in the protection of the body.

 

　　2.
Protect bones and joints.
Articular cartilage is composed of a matrix of proteoglycans, cartilage cells and collagen.
When there is external mechanical friction, it can play a role in buffering and lubricating, so that the ends of the bones slide smoothly.
Cartilage cells can produce synovial fluid that exists between articular cartilage.
The lack of proteoglycans and cartilage cells can cause structural and functional defects in bone joints, causing bone damage during movement and friction, resulting in osteoarthritis.
Glucosamine is an important nutrient that forms the intermediate of human cartilage cells and synovial fluid molecules.
It is the basic substance for the synthesis of aminoglycans and the natural tissue component of healthy joint cartilage.
With age, the body's own ability to synthesize glucosamine is getting lower and lower, and the lack of glucosamine in the body becomes more and more serious, causing continuous degradation and wear of articular cartilage.
A large number of medical studies in the United States, Europe and Japan have shown that proper supplementation of glucosamine can promote the synthesis of cartilage, inhibit the decomposition of articular cartilage, and stimulate the growth of cartilage cells.

 

　　3.
Anti-oxidation and anti-aging.
Some scholars have studied the antioxidant capacity of chitosan oligosaccharides and its protective effect on CCl4-induced liver injury in mice.
The results show that chitooligosaccharides have antioxidant capacity and have obvious protective effects on CCl4-induced liver injury in mice.
But it cannot reduce the oxidative damage of DNA.
Another study is to improve the effect of glucosamine on liver damage caused by CCl4 in mice.
The results show that glucosamine can increase the activity of major antioxidant enzymes in the liver of experimental mice, while reducing the content of AST, ALT and malondialdehyde (MDA).
, Which shows that glucosamine has a certain antioxidant capacity, but it cannot reduce the oxidative damage of CCl4 to mouse DNA.
Some scholars have studied the antioxidant properties of glucosamine and the ability to activate immune responses through various in vivo and in vitro methods.
The results show that: Glucosamine can chelate Fe2+ very well, and at the same time can protect lipid macromolecules from being oxidized and damaged by hydroxyl radicals, and has antioxidant capacity.

 

　　4.
Antiseptic and antibacterial.
Some scholars selected 21 common food spoilage bacteria as experimental strains, and studied the antibacterial effect of glucosamine hydrochloride on these 21 bacteria.
The results show that glucosamine has obvious antibacterial effects on 21 common bacteria in food, and glucosamine hydrochloride has the most obvious antibacterial effect on bacteria.
As the concentration of glucosamine hydrochloride increases, the antibacterial effect gradually becomes stronger.

 

　　5.
Used in inflammatory bowel disease (IBD).
IBD includes many intestinal diseases, such as: ulcerative colitis, chronic proctitis and Crohn's disease.
GlcN can enhance the release of acidic mucopolysaccharides from fibroblasts and restore the formation of the protective structure of the gastrointestinal mucosa.
In addition, GlcN increases the elasticity of the tissues around the blood vessels and increases the blood flow of arterial capillaries.
GlcN is also a cytoprotective agent, which can restore the integrity of human mucosa and maintain normal function.
Clinical trials have proved that GlcN has a certain effect on the treatment of IBD, and the symptoms of Crohn's disease patients have been significantly improved after oral administration of GlcN.
Therefore, GlcN is expected to become a cheap, non-toxic treatment for chronic IBD.

 

　　6.
Used in cosmetics.
The dermis is the innermost layer of the skin.
A large number of collagen, elastin and mucopolysaccharides produced by skin fibroblasts form the dermis.
Among them, collagen can keep the skin elastic and smooth.
The mucopolysaccharide is a beneficial substance to keep the skin moisturized.
Hyaluronic acid is mainly produced by fibroblasts and keratinocytes.
It retains moisture in the stratum corneum and dermis, making the skin elastic and smooth.
As a monomer of hyaluronic acid, GlcN has a smaller molecular weight than hyaluronic acid and is easier to absorb.
In addition, GlcN can also improve facial pigmentation and eliminate free radicals.
Therefore, GlcN is used in many cosmetics.
High commercial value.

 

　　Fourth, the safety of glucosamine

 

　　Studies have shown that intravenous injection of large doses of GlcN (20g) into human volunteers will not cause toxicity or changes in blood glucose concentration.
Even oral high-dose GlcN will not cause insulin disorders.
Not only that, the results of acute toxicity test, Ames test, mouse bone marrow cell micronucleus test, mouse sperm abnormality test, mouse testicular chromosomal aberration test, chronic lethal test and traditional teratogenic test on animals showed that GlcN was injected It has high safety in oral and external use.
GlcN can be used as a nutritional supplement and is widely used.

 

　　Five, the biological metabolic pathway of glucosamine

 

　　Glucosamine is essential for the biosynthesis of glycosaminoglycans (GAG).
GAG is used in animal body to combine with water to form a buffer, lubricate and protect hyaline cartilage.
Under normal circumstances, glucose produces glucosamine in the body through the hexosamine biosynthetic pathway.
Under normal physiological conditions, the content of glucosamine in extracellular fluid is lower than that of clinical testing.
If glucosamine is supplemented in the diet, glucosamine is quickly transported to cells through the glucose transport pathway, and at the same time, glucose hexaphosphate is formed through phosphorylation, thereby entering the hexosamine biosynthetic pathway.

 

　　Glucosamine is an important component necessary for the synthesis of proteoglycans in the cartilage matrix.
Proteoglycan can make articular cartilage have the function of absorbing impact force by inhibiting the stretching force of collagen fibers.
In the early stage of joint degenerative disease, the biosynthesis of agglomerated glucan is increased; in the later stage of the disease, the opposite is true.
As a result, the elasticity of cartilage is constantly weakened and many symptoms of arthritis appear gradually.
Amino monosaccharides can stimulate chondrocytes to produce glycoproteins with a normal multimeric structure, inhibit some enzymes that can damage articular cartilage (such as collagenase), prevent corticosteroids and certain non-steroidal anti-inflammatory drugs from damaging cartilage cells and Reduce the release of endotoxin factors from damaged cells.
In the development of arthritis, supplementation of exogenous glucosamine may play a beneficial role.
In in vitro experiments, if supplemented with glucosamine, the polymorphic cells that form cartilage can synthesize more aggregated glucans.
In animal models of arthritis, glucosamine also has an antioxidant effect, inhibiting the production of superoxide free radicals that damage cells.
Through the above approach, glucosamine exerts a direct anti-inflammatory effect, can relieve the painful symptoms of osteoarthritis, improve joint function, and prevent the development of the course of osteoarthritis.

　　6.
Production of Glucosamine

 

　　There are three main methods for producing GlcN, including acid hydrolysis, enzymatic hydrolysis and microbial fermentation.
The raw materials of the first two methods are basically derived from the exoskeleton of shrimp and crab, that is, chitin and chitosan are extracted from the shell of shrimp and crab, and then GlcN is obtained by acid hydrolysis or enzymatic hydrolysis.
High-concentration hydrochloric acid can degrade chitin and chitosan in shrimp and crab shells into GlcN under certain reaction conditions.
However, the large-scale use of concentrated hydrochloric acid will cause serious environmental problems, and its raw materials will be affected by regions and seasons.
limits.

 

　　The enzymatic hydrolysis method uses chitosanase to degrade shrimp and crab shells.
The biggest problem facing now is the low production efficiency, which is manifested by the high price of chitosanase, long conversion time and high production cost.
And GlcN derived from shrimp and crab shells can cause allergic reactions in patients with allergies during clinical application.

 

　　As the most potential production method, the microbial fermentation method basically overcomes the shortcomings of the above two production methods.
It has the advantages of short production cycle, high production efficiency, and less environmental pollution.
It also overcomes the restrictions on the source of raw materials in the region and seasons.
No fishy smell, no allergic reactions, etc.
Microorganisms used for fermentation can modify their metabolic pathways according to production requirements to increase the production of glucosamine.
The key enzymes that produce glucosamine and N-acetylglucosamine in microorganisms are mainly glucosamine synthase (GlmS) and glucosamine acetylase (Gna1).

 

　　At present, the production of glucosamine in microbial fermentation has become a trend in industrial production.
Compared with the enzymatic method and the chitin method, this method has many advantages.
Generally, GlcNAc is deacetylated by weak acid treatment to generate amino sugar.
Since GlcN and GlcNAc transported to the outside of the cell can be absorbed and used by the cell again, in order to increase the production of amino sugar, the relevant metabolic pathways of the cell must be modified.
The operating theory of the industrial production method is mainly to overexpress the glucosamine synthase GlmS and acetylglucosamine synthase Gna1 on the one hand; on the other hand, the enzymes that block the side branch metabolic pathways transport GlcN and GlcNAc from outside the cell to the related proteins in the cell.
Inactivation; there is also a mutation for GlmS to increase the production of amino sugar by increasing its own enzyme activity.
In addition, the optimization of fermentation conditions in the microbial fermentation process, such as the way of adding carbon sources, staged control, and regulation of fermentation temperature, will all have an impact on the accumulation of glucosamine.
The main domestic manufacturers of fermented ammonia sugar include Shandong Runde Biotechnology Co.
, Ltd.
, Anhui Yinchuang Biotechnology Co.
, Ltd.
, Zhejiang Mengjiayuan Biotechnology Co.
, Ltd.
, Shanxi Daoyi Biotechnology Co.
, Ltd.
, etc.

 

　　The strains currently used in industrial production include Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum.
Deng et al.
obtained an engineered E.
coli strain that eliminates product inhibition, so that the GlcN yield reached 17 g/L, and then Gna1 was further overexpressed, and the glucosamine yield reached 110 g/L after fermentation.
Chen Xin used E.
coli ATCC 25947 (DE3) overexpression fermentation to make the total output of glucosamine reach 132.
43 g/L.
With the enhancement of people’s safety awareness, the most popular glucosamine-producing strain is Bacillus subtilis.
Liu Yanfeng used Bacillus subtilis 168 as the starting strain to over-express the gene Glms and gene gna1, and realized the GlcNAc in Bacillus subtilis.
Accumulation finally made the yield of GlcNAc reach 31.
65 g/L.
The yield of N-acetylglucosamine produced by Wang Yating using Corynebacterium glutamicum by fermentation reached 2.
23 g/L.

 

　　Nowadays, glucosamine has been widely used as a health food in the world, and it ranks among the best in the nutrition and health food sales section of major e-commerce companies.
Its products have global sales of 2 billion U.
S.
dollars.
At present, domestic production is mainly based on traditional methods, which are obtained by hydrolyzing chitin acid extracted from crab shells and shrimp shells.
The polymer is mainly decomposed by concentrated hydrochloric acid to form glucosamine.
However, as the aging population of Chinese society continues to increase and the demand for glucosamine continues to increase, the output extracted by the hydrolysis method will be limited by changes in the supply of raw materials.
In addition, products with raw materials derived from shellfish will have a certain fishy taste, and the high protein of shellfish is not suitable for people with allergic symptoms.
The traditional method of producing glucosamine can no longer meet people's needs.
The microbial production method has received widespread attention due to its advantages, and has made considerable progress.
Although recombinant E.
coli has made great breakthroughs in the production of glucosamine by fermentation, the gram-positive bacterium Bacillus subtilis, as a safer host bacteria, is expected to replace E.
coli and become a high-yield engineered strain of glucosamine.
And based on more advantages in safety, it is expected to be applied on a large scale in food and medicine.