How do hyperuricemia and gout diseases occur?
Uric acid (molecular formula is C5H4N4O3) is the final product of the metabolism of purines in primates, including humans, about 80% of uric acid in the human body is metabolized in the body, and about 20% comes from the decomposition of food contained in the purine or nucleoprotein components of the food ingested by the human body.
Some people have the deletion of certain inherited genes or because of diseases (such as obesity, hyperglycemia, hypertension, hyperlipidemia and other metabolic diseases), taking drugs to treat certain diseases and a penchant for high-purine foods, which will lead to obstruction of uric acid excretion in the human body or increased uric acid content in the body.
However, if the uric acid in the body exceeds saturation, it will lead to hyperuricemia, and will precipitate urate crystals in the body, precipitate in the joints or tissues, which will cause an inflammatory response and lead to gout.
Urate deposited in the kidneys or/and ureters can lead to gouty nephropathy or renal failure, which is severely life-threatening.
How is uric acid, which causes you to have recurrent attacks of gout, produced in the body?
Uric acid is an organic compound, while xanthine is an intermediate product of uric acid metabolism, while xanthine can be formed by hypoxanthine formed by hypoxanthine nucleotides, and xanthine can also be formed after guanine deamination.
Xanthine is converted in cytosol to uric acid by xanthine oxidase.
Uric acid is converted into allantoin and carbon dioxide by urase in non-primates in peroxisomes, which are excreted.
But in primates over the long course of evolution, the gene responsible for expressing uridase was evolved (or became a pseudo-gene, that is, an invalid gene), so that after purine was metabolized to uric acid, it was not further decomposed.
The entire process of purine metabolism into uric acid, as shown in the figure above.
When uric acid production and excretion are unbalanced, and the serum uric acid concentration in the body continues to rise, hyperuricemia and gout can be caused.
From the production of uric acid in the human body, see how uric acid hypergoma people can effectively lower uric acid
From the above analysis, we know that there will be a series of precursors and enzymes in the production process of uric acid, so based on this principle, we can think about how to reduce blood uric acid from affecting the production of uric acid in the body.
1. Inhibits the activity of key enzymes in uric acid production to reduce uric acid:
Uric acid is mainly produced in the human liver, and from the above schematic diagram of purine metabolism into uric acid, we can see that in the whole process of purine metabolism to produce uric acid, the two key enzymes that catalyze and regulate uric acid production are: adenosine deaminase and xanthine oxidase.
If the activity of these two enzymes can be affected or inhibited, can uric acid production be controlled and thus reduced in the body?
First, let's talk about adenosine deaminase, which is one of the important catalytic enzymes in the process of adenylate metabolism, which indirectly regulates uric acid production. Adenosine deaminase is an enzyme involved in purine metabolism that catalyzes the release of adenosine or 2-deoxyadenosine water from ammonia into inosine (also known as hypoxanthine nucleoside) or 2-deoxyinosine. Inosine is continuously catalyzed by nucleoside phosphorylase and xanthine oxidase to produce uric acid.
Now we know that adenosine deaminase is also a potential target for the treatment of lymphoproliferative diseases and cancer, so if the adenosine deaminase is inhibited, it can not only reduce uric acid production, reduce blood uric acid, but also have anti-tumor effects.
Xanthine oxidase, is the last key enzyme in the formation of uric acid in the human body, its molecular weight size of about 300 kDa dimer, and then purine metabolism process directly regulate uric acid synthesis.
Among them, the center of molybdenum butterfly is the key site of xanthine oxidase catalyzing xanthine to form uric acid, which can specifically identify and bind to the nitrogen-containing aromatic heterocyclic rings of xanthine and/or hypoxanthine, so that the structure of xanthine oxidase changes, from the continuous catalytic oxidation of hypoxanthine and xanthine to uric acid.
Hydrogen peroxide and superoxide radicals are also produced during the reoxidation of hypoxanthine and xanthine, which are catalyzed by superoxide dismutase to superoxide and converted to hydrogen peroxide. If excess xanthine oxidase activity leads to the accumulation of uric acid in the body in the tissues, uric acid can also be combined with the production of reactive oxygen species to regulate the inflammatory pathway.
Therefore, by inhibiting xanthine oxidase, it is the primary treatment to inhibit uric acid synthesis and thus reduce uric acid levels in the body and reduce gout inflammation and itching.
Based on this principle, the uric acid-lowering drugs allopurinol and febustat were thus born.
2. Promote the decomposition of uric acid prerequisites, truncate the uric acid production pathway and lower uric acid:
From the above schematic diagram of the purine metabolism process, it is known that the premise of uric acid includes purines, nucleotides, nucleotides, inosine and other intermediate substances, which are finally formed after being catalyzed by the corresponding enzymes.
If these intermediate precursors that form uric acid can be decomposed, the uric acid content of human metabolism can also be reduced, reducing uric acid production, so as to achieve the purpose of reducing uric acid in the body and preventing gout.
3. Promote the decomposition of uric acid, thereby reducing the concentration of uric acid:
Uric acid lowering can also lower uric acid in the body by directly breaking down uric acid, which is oxidized to allantoin and carbon dioxide.
Therefore, by taking or injecting bioactive substances that can degrade uric acid, decomposing uric acid in the blood and reducing uric acid production, it can effectively reduce the concentration of uric acid in the serum.
However, this method, although effective, is very dangerous and is generally not used.
In short, our goals are: uric acid is no longer high, gout will not be committed, away from kidneys and urinary stones.
More than a year of headline science, the more communication with fans, gradually put the focus of science on metabolic diseases, especially gout, because of the deep experience of gout people's joys and sorrows. So Dr. Jiang has a wish in 2022 to recruit 1,000 patients with gout for many years to work with me to correctly lower uric acid away from the shackles of gout, which can be answered one-on-one. Those who want to register can pay attention to @ Chinese medicine Dr. Jiang to chat about gout after the private message reply "registration" message.
References in this article (picture from the Network, invasion and deletion): Jiang Linhong, No. 8, 2020, Journal of Food and Machinery, and other articles "Research Progress on the Mechanism of Action of Uric Acid-Lowering Natural Bioactive Substances".
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