What Is a Vitamin B12 Toxicity?

Vitamin B12, also called cobalamin, is the only vitamin that contains metal elements. Vitamin B12 in nature is synthesized by microorganisms, and higher plants and animals cannot make vitamin B12. Vitamin B12 is the only vitamin that needs the help of an intestinal secretion (endogenous factor) to be absorbed. Some people suffer from gastrointestinal abnormalities and lack this endogenous factor, even if they have sufficient sources in the diet, they will develop pernicious anemia. Vitamin B12 is essentially absent from plant foods. It stays in the intestines for a long time and takes about three hours (most water-soluble vitamins only take a few seconds) to be absorbed. The main physiological function of vitamin B12 is to participate in the production of bone marrow red blood cells, prevent malignant anemia, and prevent brain nerves from being damaged. Vitamin B12 is the latest found among B vitamins to date. Vitamin B12 is a polycyclic compound containing trivalent cobalt. Four reduced pyrrole rings are linked together to form a glutinate ring (similar to porphyrin), which is the core of the vitamin B12 molecule. Therefore, compounds containing this ring are all called corrinoids. Vitamin B12 is a light red needle-like crystal that is easily soluble in water and ethanol. It is most stable under the conditions of pH 4.5 to 5.0. It decomposes in strong acid (pH <2) or alkaline solution. It can be destroyed to a certain extent when exposed to heat. However, the loss of high-temperature disinfection in a short time is small, and it is easy to be damaged when exposed to strong light or ultraviolet rays. Loss of about 30% during normal cooking.

Vitamin B12, also called cobalamin, is the only vitamin that contains metal elements. Vitamin B12 in nature is synthesized by microorganisms, and higher plants and animals cannot make vitamin B12. Vitamin B12 is the only vitamin that needs the help of an intestinal secretion (endogenous factor) to be absorbed. Some people suffer from gastrointestinal abnormalities and lack this endogenous factor, even if they have sufficient sources in the diet, they will develop pernicious anemia. Vitamin B12 is essentially absent from plant foods. It stays in the intestines for a long time and takes about three hours (most water-soluble vitamins only take a few seconds) to be absorbed. The main physiological function of vitamin B12 is to participate in the production of bone marrow red blood cells, prevent malignant anemia, and prevent brain nerves from being damaged. Vitamin B12 is the latest found among B vitamins to date. Vitamin B12 is a polycyclic compound containing trivalent cobalt. Four reduced pyrrole rings are linked together to form a glutinate ring (similar to porphyrin), which is the core of vitamin B12 molecule. Therefore, compounds containing this ring are all called corrinoids. Vitamin B12 is a light red needle-like crystal that is easily soluble in water and ethanol. It is most stable under the conditions of pH 4.5 to 5.0. It decomposes in strong acid (pH <2) or alkaline solution. It can be destroyed to a certain extent when exposed to heat. However, the loss of high-temperature disinfection in a short time is small, and it is easy to be damaged when exposed to strong light or ultraviolet rays. Loss of about 30% during normal cooking.

Chinese name: Vitamin B12
English name: Vitamin B12
nickname: Cobalamin, cyanocobalamin, animal protein factors, anti-malignant vitamins

Chemical formula: C63H88CoN14O14P
Molecular weight: 1355.37
EINECS: 200-680-0

Structural Features of Vitamin B12

Glutamyl and methylglutamine are two coenzyme forms of B12. Cobalt ions are linked to the N-3 of 5,6-2 methylphenylimidazole above the plane of the cobalt ring, and to C5 'of 5'-deoxyadenosine below the plane. B12, which is commonly used, is connected to cobalt ions, which is called cyanocobalamin, which is a green crystal.

Vitamin B12 physiological effects

Vitamin B12 effect

B12 is known as a coenzyme of several mutases, such as methylaspartate mutase that catalyzes the conversion of Glu to methyl Asp, and methylmalonyl catalyzes the conversion of methyl malonyl CoA to succinyl CoA CoA mutase. B12 coenzyme also participates in the transfer of methyl and other one-carbon units.

B12 mainly exists in meat. Soy in plants and some herbs also contain B12. Intestinal bacteria can be synthesized, so it is not deficient in general. However, B12 is a vitamin that is easily lacked by people with digestive diseases, and it is also indispensable for red blood cell production. Important elements, if severely lacking, will lead to pernicious anemia!

Vitamin B12 is widely found in animal foods. And its form cannot be absorbed by the human body. In addition, vitamin B12 is also the only vitamin that contains essential minerals. It is red because of its cobalt content, also known as red vitamins. It is one of the few colored vitamins. Although vitamin B12 is a B group vitamin, it can be stored in the liver. After the storage capacity is exhausted, symptoms of deficiency occur after more than half a year. The human body needs very little vitamin B12, as long as the diet is normal, it will not be lacking. A few people with malabsorption need special attention.

Vitamin B12 absorption and metabolism

Vitamin B12 in food combines with proteins and enters the human digestive tract. Under the action of gastric acid, pepsin, and trypsin, vitamin B12 is released and binds to an internal glycoprotein (IF) secreted by gastric mucosal cells. Vitamin B12-IF complex is absorbed in the ileum. Vitamin B12 is stored in small amounts, about 2 to 3 mg in the liver. It is mainly excreted from urine and partly from bile.

Vitamin B12 physiological function

There are two main: As cofactors of methyltransferases, they are involved in the synthesis of methionine, thymine, etc., such as converting methyltetrahydrofolate to tetrahydrofolate and transferring the methyl group to the methyl acceptor (like the type half Cysteine), so that the methyl acceptor becomes a methyl derivative (such as methionine or methyl homocysteine), and the reaction is shown in the figure. Therefore, vitamin B12 can promote the biosynthesis of protein and affect the growth and development of infants and young children when lacking. Protect the transfer and storage of folic acid in cells. When vitamin B12 is deficient, human red blood cells have low folate content, and the folate stored in the liver decreases. This may be related to the lack of vitamin B12, which causes the difficulty in transferring methyl groups from homocysteine to methionine. The methyl groups accumulate in the cells and damage Intracellular storage of tetrahydrofolate, because tetrahydrofolate tends to combine with methyl to form methyltetrahydrofolate, which synthesizes polyglutamic acid.

Vitamin B12 main functions

1.Promote methyl transfer

2. Promote the development and maturation of red blood cells, keep the body's hematopoietic function in a normal state, prevent pernicious anemia, and maintain the health of the nervous system

3. Exist in the form of coenzyme, which can increase the utilization of folic acid and promote the metabolism of carbohydrates, fats and proteins

4, with the role of activating amino acids and promote the biosynthesis of nucleic acids, can promote the synthesis of proteins, it has an important role in the growth and development of infants and young children

5. Metabolize fatty acids so that fat, carbohydrates and proteins are properly used by the body

6. Eliminate irritability, focus attention, enhance memory and balance

7. It is an indispensable vitamin for the sound function of the nervous system and is involved in the formation of a lipoprotein in neural tissues.

The first is to improve the utilization of folic acid, synthesize methionine (synthesized from homocysteine) and choline with folic acid, and synthesize precursors of cyanocobalaminyl such as methylcobalamin and coenzymes in the process of producing purines and pyrimidine B12, involved in the methylation process of many important compounds. When vitamin B12 is deficient, the activity of transferring methyl groups from methyltetrahydrofolate is reduced, making folic acid into an unusable form, resulting in folic acid deficiency.

The second is to maintain the metabolism and function of the nerve myelin sheath. Lack of vitamin B12 can cause neurological disorders, spinal cord degeneration, and severe mental symptoms. Vitamin B12 deficiency can cause peripheral neuritis. The early manifestations of a child's lack of vitamin B12 are abnormal mood, sluggish expression, and unresponsiveness, leading to anemia.

The third is to promote the development and maturation of red blood cells. Methylmalonyl-CoA is converted into succinyl-CoA and participates in the tricarboxylic acid cycle, in which succinyl-CoA is involved in the synthesis of heme.

Fourth, vitamin B12 also participates in the synthesis of DNA, the metabolism of fats, carbohydrates and proteins, increasing the synthesis of nucleic acids and proteins.

pathology

Vitamin b12 and folic acid deficiency, thymine nucleotides are reduced, DNA synthesis is slowed, and intracellular uracil deoxynucleotides (dUMP) and deoxyuridine triphosphate (dUTP) are increased. Thymine deoxynucleotide triphosphate (dTTP) is reduced, so that uracil is incorporated into the DNA, the DNA is fragmented, DNA replication is slowed, and the mitotic time is prolonged (S and G1 phases are prolonged). Chromatin has a network of loose spots and lacks concentration. There is no obvious obstacle to RNA and protein synthesis in cytoplasm. With the delay of mitotic division and the increase of the synthesis amount, the formation of huge soma, the development of nuclear plasma is not synchronized, the nuclear chromatin is loose, the so-called "old plasma young nucleus" changed giant blood cells. The giant change is the most significant and characteristic of the juvenile red blood cell series, which is called the juvenile red blood cell series. Giant changes in cell morphology are also seen in granulocytes, megakaryocytes, and even some proliferative somatic cells. The giant juvenile red blood cells are easily destroyed in the bone marrow, and invalid red blood cells appear. Eventually, the number of red blood cells is insufficient, and symptoms of anemia appear.

Vitamin B12 deficiency supplement

Vitamin B12 deficiency symptoms

Vitamin B12 deficiency causes pernicious anemia (3 photos)

Malignant anemia (insufficient red blood cells)

Irregular menstruation

Yellow eyes and skin, local (small) redness and swelling (not painful and itchy) accompanied by molt;

nausea, loss of appetite, weight loss

Pale lips, tongue and gums, bleeding gums

headache, memory loss, dementia

He may cause mental depression,

Causes nucleated giant red cell anemia (malignant anemia)

Deformation of spinal cord, degeneration of nerves and peripheral nerves

Inflammation of the mucous membranes of the tongue, mouth, and digestive tract.

If symptoms such as loss of appetite, indigestion, inflammation of the tongue, loss of taste, etc., are a warning sign of vitamin B 12 deficiency

The early manifestation of vitamin B12 deficiency in children is symptoms of mental and emotional abnormalities, sluggish expression, less crying, less responsiveness, slowness to sleep, and love to sleep, which will eventually cause anemia.

13. Increased risk of heart disease.

Vitamin B12 deficiency is mostly caused by malabsorption, and dietary vitamin B12 deficiency is rare. Dietary deficiencies are found in vegetarians, and vitamin B12 deficiency occurs due to not eating meat. Too little gastric acid can cause malabsorption of vitamin B12 in the elderly and patients with gastrectomy. ^[1-3]

Side effects : Some patients have allergic reactions to the product, and even anaphylactic shock. Pay attention when using it.

Vitamin B12 nutrition level identification

The identification methods are: The determination of serum vitamin B12 is the most direct identification method. A serum vitamin B12 concentration of less than 100 g / ml can be diagnosed as a vitamin B12 deficiency (normal value is 100-300 g / ml). The measurement of urinary methylmalonic acid is an indirect method. When vitamin B12 is lacking, the excretion of urinary methylmalonic acid increases due to special metabolic disorders, but it does not increase when folic acid is lacking. Vitamin B12 deficiency and folic acid deficiency. Vitamin B12 absorption test. Vitamin B122.0 g labeled with radioactive cobalt was administered orally to the subject, while 1000 g of vitamin B12 was intramuscularly injected, and then the radioactivity of urine was measured within 48 hours. Those with normal absorption of vitamin B12 can excrete 5 to 40% of oral radioactive cobalt within 48 hours; those with defective absorption of vitamin B12 (such as malignant anemia, after gastrectomy, and tropical nutritional megaloblastic anemia) have less than 5%. The therapeutic test is the earliest, simplest and most convenient diagnostic method used in clinical work. This method can be used when the conditions for conducting the above-mentioned various tests are not available. After treatment with vitamin B12, the red blood cells of the reticulum rise, and at the same time, the juvenile red blood cells in the bone marrow transform into red blood cells of normal form, which can be judged as vitamin B12 deficiency.

The main source of vitamin B12 in the body

Food: animal liver, kidney, beef, pork, chicken, fish, clams, eggs, milk, cheese, dairy products, bean curd

Drug: Vitamin B 12 is not easily absorbed by the stomach, most of it is absorbed through the small intestine, so long-acting lozenges work better

When there is a serious deficiency of vitamin B 12, the doctor will usually supplement it by injection

It is difficult for the elderly to absorb vitamin B 12 and can be supplemented by injection at the hospital. Insufficient vitamin B12 levels in the elderly population are extremely common, and attention should be paid in time, otherwise it will reduce cognitive ability and accelerate the development of Alzheimer's disease.

Vitamin B12 food sources

Vitamin B12 in nature is mainly synthesized by bacteria in the rumen and colon of herbivores. Therefore, its dietary sources are mainly animal foods, among which animal viscera, meat, and eggs are rich sources of vitamin B12. Soy products produce a part of vitamin B12 after fermentation. Human intestinal bacteria can also synthesize a part. ^[3]

Cosmetic application

Vitamin B12 is generally called a hematopoietic vitamin. It has the superior effect of skin regeneration. It is indispensable for cell regeneration and hematopoietic. It is an important component to promote human metabolism.

Vitamin B12 is the latest type of vitamin. All the vitamins were found last. The molecular composition is the most complicated. The content of vitamin B12 in the human body will gradually decrease with increasing age, especially women will decrease rapidly due to their physiological structure.

Easily solve the following skin problems:

* Skin problems such as tired, dull and dry skin;

* Visibly reduces the appearance of fine lines and wrinkles due to age;

* Repair skin redness, peeling, and pain caused by sun, dry and cold in autumn and winter;

* Acne scars, scars from mosquito bites, burns and burns;

* Use after plastic surgery to avoid leaving scars.

Vitamin B12 main uses

Vitamin B12 medical aspects

For the treatment and prevention of vitamin B12 deficiency.

For gastrectomy or malabsorption syndrome, vitamin B12 deficiency can prevent anemia.

It is used to supplement the increased demand for vitamin B12 caused by wasting diseases, hyperthyroidism, pregnancy, breastfeeding, etc.

Nutritional and pregnancy anemia.

Anaemia of broad head split head tsutsugamushi disease.

Anemia of liver disorders.

Leucopenia caused by tritium radioactivity.

Sacral nerve pain, muscle pain, joint pain.

Peripheral neuritis, paralysis of peripheral nerves.

Myelitis, spinal cord degeneration.

Vitamin B12 feed additive

Vitamin B12 is an indispensable micronutrient for the growth of the body. Most animal's plant-based feed does not contain vitamin B12. On the one hand, animals rely on the synthesis of microorganisms in the gastrointestinal tract and on the other hand, they are added from the outside. In order to meet the needs of animal vitamins, vitamin additives must be supplemented.

The lack of vitamin B12 in non-ruminant animals such as pigs and chickens is mainly due to growth retardation, and a few pigs may have mild normal red blood cell anemia. In addition, the hatchability of chickens and the fertility of pigs can be reduced. The clinical symptoms of deficiency include loss of appetite, growth arrest, simple anemia, and severe neurological symptoms.

Feed vitamin B12 can promote the growth and development of poultry, especially young birds and young animals.

can be use on:

Poor growth and anemia caused by vitamin B12 deficiency in pigs and chickens;

Endemic wasting in cattle and sheep in areas lacking cobalt;

non-specific treatment of neuritis and neuralgia;

Improve the utilization rate of feed protein;

The breeding of economic animals;

Treating fish eggs or fry with B12 solution can improve the tolerance of fish to toxic substances in water such as benzene and heavy metals.

Vitamin B12 other

Food additives

Can be used as food colorant: such as ham, sausage, ice cream, fish sauce.

Used in cosmetics, soap, toothpaste, etc., and also used in toilets, refrigerators, oral cavity, etc. to deodorize and eliminate the smell of sulfide and aldehyde.

Detoxification of air pollutants

Scientists at the University of Manchester in the United Kingdom have achieved a major breakthrough in a 15-year study. They hope that the results will promote research and development of hazardous air pollutants such as polychlorinated biphenyls (PCBs) and dioxins. Effective method of poisoning. The details of the study, published in the journal Nature, describe how certain organisms reduce pollutant toxins.

A team from the University of Manchester's Institute of Biotechnology has investigated how certain natural organisms reduce toxin levels and shorten the lifespan of severe pollutants.

Professor David Rice explained: "We already know that some of the most toxic pollutants contain halogen atoms, and most biological systems don't know how to deal with these molecules. However, some organisms can use vitamin B12 to remove these halogens. Atoms. Our research has determined that they use vitamins in very different ways than we know. " ^[4]

Vitamin B12 synthetic

Woodward's Most Outstanding Achievement, Synthesis of Vitamin B12

In 1965, Woodward was awarded the Nobel Prize in Chemistry for his outstanding contribution to organic synthesis. After winning the award, he did not stop working because of his success. Instead, he is moving towards more difficult and complex chemical synthesis. "He organized 110 chemists from 14 countries to work together to explore the artificial synthesis of vitamin B12. Before him, this extremely important drug could only be obtained from The internal organs of animals are artificially refined, so they are extremely expensive and in short supply.

The structure of vitamin B12 is extremely complicated. Woodward has found that it has 181 atoms and is distributed in a magic felt shape in space. It is extremely fragile and will decompose under the action of strong acids, alkalis, and high temperatures. Great difficulty. Woodward designed a splicing synthesis scheme that synthesizes various parts of vitamin B12 first and then docks them together. This method later became the common method for the synthesis of all organic macromolecules.

In the process of synthesizing vitamin B12, not only a problem of creating a new synthetic technology, but also an organic theoretical problem that cannot be explained by traditional chemical theory. To this end, Woodward referred to the "boundary electron theory" proposed by the Japanese chemist Kenichi Fukui, together with his student and assistant Huffman, proposed the principle of conservation of molecular orbital symmetry. This theory uses symmetry to simply and intuitively Explained many organic chemistry processes, such as electrocyclization reaction process, cycloaddition reaction process, bond migration process, etc. The principle states that when the orbits of the reactant molecules are symmetrical, the reaction is easy to proceed. This is called "symmetry allows". When the orbits of the reactant molecules are not symmetrical, the reaction is not easy to proceed. . The establishment of molecular orbital theory enabled Huffman and Kenichi Fukui to jointly win the Nobel Prize in Chemistry in 1981. Because at the time, Woodward had died for 2 years, and the Nobel Prize was not awarded to deceased scientists. Therefore, the academic community believes that if Woodward is still alive, he must be one of the winners, so he will become One of the few scientists to receive a Nobel Prize twice.

Woodward did nearly a thousand complex organic synthesis experiments when synthesizing vitamin B12. It took 11 years, and it was finally realized a few years before he died, completing the complex vitamin B12 synthesis work. In addition to the chemists who participated in the synthesis of vitamin B12, in addition to Huffman, there are also well-known Swiss chemists A. Escheni11oser.

Vitamin B12 industrial manufacturing

The industrial manufacture of vitamin B12 is made by microbial fermentation ^[5]

Streptomyces griseus has been a source of vitamin B12 for many years. Usually from Pseudomonas denitrificans and Propionibacterium shermanii . They generally need to be cultured under special conditions to increase yield. The world's major vitamin B12 producers are in China, of which Hebei Yuxing Bioengineering Co., Ltd. has the largest output in the world, accounting for nearly 70% of the global VB12 production, and has been certified by the US FDA Drug Administration in the early days. Products are exported to countries all over the world.

In 2014, the total output of vitamin B12 in the world was about 50 tons. Most products are used in vitamin B12 preparations and animal feed additives.

Vitamin B12 Pharmacology

Vitamin B12 pharmacodynamics

Vitamin B12 is a red compound containing cobalt, which needs to be converted into methylcobalamin and coenzyme B12 before it is active. Folic acid in the body must be reduced to dihydrofolate through reduction, and then under the action of dihydrofolate reductase, it becomes tetrahydrofolate. Methylcobalamin can convert tetrahydrofolate to N5, N10-methenyltetrahydrofolate, which has the function of supplying a "one carbon group" during the conversion of uracil deoxynucleotides. N5, N10-methenyltetrahydrofolate reductase can catalyze the reduction of N5, N10-methenyltetrahydrofolate to N5-methenyltetrahydrofolate. With the participation of methylcobalamin, N5-methenyltetrahydrofolate removes the methylenyl group and becomes tetrahydrofolate, while the methylenyl group is transferred to homocysteine to form methionine. In this way, the body must maintain a sufficient amount of tetrahydrofolate for large amounts of DNA synthesis. Therefore, in the absence of vitamin B12, its hematological effect is similar to that of folic acid, that is, DNA synthesis is blocked, resulting in megaloblastic anemia. So vitamin B12 is indirectly involved in thymine deoxynucleotide synthesis. The conversion of methylmalonyl-CoA to odd-saturated fatty acids and certain amino acids into succinyl-CoA must involve the participation of methylmalonyl-CoA mutase and coenzyme B12. When the human body lacks vitamin B12, it can cause increased excretion of methylmalonic acid and abnormal metabolism of fatty acids. If methylmalonic acid is deposited in nerve tissue, it may denature it. S-adenosylmethionine and methionine are mainly formed by homocysteine accepting the methyl group of N5-methyltetrahydrofolate. Methyl vitamin B12 is the coenzyme of the above reaction. Therefore, the lack of vitamin B12 can lead to the synthesis of methionine and S-adenosylmethionine, which may be one of the causes of neurological diseases.

Vitamin B12 Pharmacokinetics

Oral vitamin B12 forms a vitamin B12-internal factor complex in the stomach with internal factors secreted by gastric mucosal parietal cells. When the complex enters the terminal end of the ileum, it binds to the receptors on the microvilli of the ileal mucosal cells, enters the intestinal mucosal cells through the puffing effect, and then absorbs the blood. The blood concentration reached a peak 8 to 12 hours after oral administration; about 40% of the blood concentration was absorbed into the blood at 40 minutes after intramuscular injection. After intramuscular injection of 121 mg of vitamin B, the average time of blood concentration above 1ng / ml was 2.1 months. Vitamin B12 is absorbed into the blood and combined with transcobalamin, which is transferred into the tissue. There are three types of transcobalamin, of which transcobalamin II is the main form of vitamin B12 transport, accounting for 2/3 of the total content of vitamin B12 in plasma. The liver is the main storage site for vitamin B12. The total amount of vitamin B12 stored in the human body is 3 ~ 5mg, of which 1 ~ 3mg is stored in the liver. Vitamin B12 was taken orally, and the concentration of vitamin B12 in the liver reached a peak after 24 hours. After 5 to 6 days, about 60 to 70% of the useful amount is still concentrated in the liver. Mainly through the kidneys, except for the body's demand, a few breaths are excreted in the original shape with the urine. After intramuscular injection of 121 mg of vitamin B, 72 hours later, 75% of the total amount was excreted as urine. Urinary excretion increases with the injection volume. After intramuscular injection of 5 g, 3 to 4 g is excreted in 8 hours; after intramuscular injection of 1 mg, 8 hour excretion can reach 330 to 470 g.