Introduction

Vitamin B12 is a group of cobalt-containing biologically active substances called cobalamins, which include cyanocobalamin, hydroxycobalamin and two coenzyme forms of vitamin B12: methylcobalamin and adenosylcobalamin. In most cases, vitamin B12 is cyanocobalamin.

Cobalamin is one of the important vitamins for the human body. This amazing bioactive compound has unique properties that plays an important role in many physiological processes in the human body.

Vitamin B12 has a unique ability to affect many biological processes such as red blood cell formation, the nervous system, lipid and amino acid metabolism. Its deficiency can lead to serious diseases and disorders in the body.

Apart from its important role in the biochemical processes of the body, vitamin B12 also has some unusual properties. The cyanocobalamin molecule is the largest among the molecules of all vitamins. Almost all vitamins can be obtained from various plants or animals, but no plant or animal can produce vitamin B12. The exclusive source of this vitamin, according to current evidence, is tiny microorganisms: bacteria, yeast, molds and algae. Vitamin B12 can be produced artificially through biotechnology using special bacterial cultures, making it available for medical use and scientific research.

The successful complete synthesis of a compound of such a complex structure was an outstanding achievement of synthetic organic chemistry and demonstrated in practice the fundamental possibility of chemical synthesis of “any” natural compound, regardless of the complexity of the structure of its molecule.

Physical and Chemical Properties of Vitamin B12

Vitamin B12 (cyanocobalamin) is a chemical compound with the chemical formula C₆₃H₈₈CoN₁₄O₁₄P. It is a solid crystal of dark red color, odorless. The molecular weight of cyanocobalamin is 1355.38 g/mol. It has a melting point > 300°C, a bulk density of 400-800 kg/m³ and is sparingly soluble in water (1.25 g dissolves in about 100 ml at 25°C) and in ethanol, insoluble in acetone, ether and chloroform.

Synthesis of Vitamin B12

Vitamin B12 can be obtained from natural sources and by using synthetic methods. Natural synthesis of vitamin B12 is carried out in microorganisms such as bacteria and algae, which can biosynthesize this vitamin. Chemical synthesis methods are sometimes used for scientific research.

The synthesis of vitamin B12 is a complex and multi-stage process that requires the participation of various organic compounds. The complete synthesis of the complex biomolecule vitamin B 12 was carried out by two different methods, by the research groups of Robert Burns Woodward and Albert Eschenmoser in 1972 and took almost 12 years to obtain.

Chemical Synthesis of Vitamin B12

The process of synthesis vitamin B12 consists of many stages. Main stages:

Stages of cobiric acid synthesis. Two methods have been developed, but they differ mainly in the way they construct the central macrocyclic system of corrin ligands.

And stages of vitamin B12 reduction from cobiric acid by step-by-step construction of the nucleotide part of the vitamin. If necessary, a form of vitamin B12, methylcobalamin can be synthesized by reducing cyanocobalamin in the laboratory with sodium borohydride in an alkaline solution followed by the addition of iodomethane.

Microbiological Synthesis of Vitamin B12

Of all the vitamins, vitamin B12 and its coenzyme form are primarily produced by microbiological synthesis. Propionic acid bacteria serve as producers in this process.

Propionibacterium has a variety of practical applications. Propionibacterium freudenreichii subsp. shermanii is a major crop used in the world’s cheese production and in the production of vitamin B12.

To obtain vitamin B12, bacteria are periodically cultivated under anaerobic conditions in a corn extract, glucose, cobalt salts and ammonium sulfate. The acids formed during fermentation are neutralized by an alkaline solution, which is continuously fed into the tank. Fermentation ends after 72 hours. Vitamin B12 is stored in bacterial cells. Therefore, after fermentation is completed, the biomass is separated and vitamins are extracted from it with water acidified to pH 4.5 – 5.0 at a temperature of 85-90°C for 60 minutes with the addition of 0.25% sodium nitrite as a stabilizer.

The biosynthesis of vitamin B12 is discussed in detail in the video:

Vitamin B12 (Cobalamin) Biosynthesis

Functions of Vitamin B12

Vitamin B12 is involved in the conversion of folic acid into its active form, in the synthesis of methionine, coenzyme A, the antioxidant glutathione, succinic acid and myelin. It controls DNA synthesis (cell division), maturation of red blood cells, increases the level of T-suppressors, which helps limit autoimmune processes.

Vitamin B12 and Formation of Red Blood Cells.

The best-known function of vitamin B12 is its role in the development of red blood cells. Vitamin B12 is responsible in the body for maintaining normal hematopoiesis. Without vitamin B12 it is impossible to obtain the information necessary for the formation of red blood cells. The cells become too large and begin to function ineffectively, a condition called pernicious anemia.

Vitamin B12 and the Nervous System

The second task of vitamin B12 is its participation in the development of nerve fibers. Vitamin B12 is involved in the construction of protein and fatty structures of the protective myelin layer. The myelin sheath that covers neurons forms less successfully when there is a vitamin B12 deficiency. Although vitamin B12 plays an indirect role in this process, vitamin B12 supplementation has been shown to be effective in relieving pain and other symptoms of nervous system disorders.

Another of the main tasks of vitamin B12 is participation in the production of methionine, an amino acid that affects mental performance and the formation of a person’s emotional background. Vitamin B12, folic acid and methionine form a kind of working group that specializes mainly in the functioning of the brain and the entire nervous system. These substances are involved in the production of so-called monoamines – stimulants of the nervous system.

Also, vitamin B12 and folic acid contribute to the production of choline, which significantly affects mental activity and psyche. During metabolism, the neurotransmitter acetylcholine is produced from it in the so-called cholinergic fibers. When a person needs to concentrate, the accumulated choline is converted into acetylcholine, which activates the brain.

Vitamin B12 and Metabolism

Vitamin B12 is essential for circulating proteins in the body that are necessary for cell growth and repair. Many of the key components of protein, called amino acids, become unusable in the absence of B12. Vitamin B12 affects the movement of carbohydrates and fats in the body. In combination with folic acid (vitamin B9) and pyridoxine (vitamin B6), vitamin B12 normalizes the metabolism of methionine and choline, thereby having a beneficial effect on the liver.

Deficiency of Vitamin B12

Symptoms potentially associated with vitamin B12 deficiency: dandruff, decreased blood clotting, numbness in the legs, decreased reflexes, difficulty swallowing, tongue ulcers, fatigue, tingling in the legs, menstrual irregularities.

The rate at which B12 levels change depends on how much B12 is taken in from food, how much is excreted from the body, and how much is absorbed. In young children, B12 deficiency can appear much more quickly. Older adults are at high risk of developing B12 deficiency due to decreased stomach acid and decreased cell function. Up to 100% of vitamin B12 obtained from food can be excreted in the feces.

Conclusion

Vitamin B12 with its unique chemical properties, biological activity and diverse functions in the body, plays an indisputable role in maintaining the health of humans and living organisms. Its importance ranges from participation in biochemical reactions of methylation and amino acid metabolism to regulation of red blood cell formation and maintenance of the nervous system.

Medical practice and scientific research have proven its efficacy in the treatment of various diseases and its use in biochemical research. However, as with any bioactive substance, it is important to maintain a balance of vitamin B12 in the body, avoiding excesses or deficiencies, which can lead to health consequences. Further research and practical applications of vitamin B12 continue to expand our knowledge and its value as a key element in biology and medicine.

Bibliography

• Vitamin B12 A. David Smith, Martin J. Warren, Helga Refsum, Advances in Food and Nutrition Research Volume 83, 2018, Pages 215-279 https://doi.org/10.1016/bs.afnr.2017.11.005
• Vitamin B12 Deficiency Sally P. Stabler, M.D. The New England Journal of Medicine, 2013; 368:149-160 https://www.nejm.org/doi/full/10.1056/nejmcp1113996
• Chemistry and Enzymology of Vitamin B12 Kenneth L. Brown Chem. Rev. 2005, 105, 6, 2075–2150 Publication Date: April 2, 2005 https://doi.org/10.1021/cr030720z
• The Structure of Vitamin B12 Dorothy Crowfoot Hodgkin, Jennifer Kamper, June Lindsey, Maureen MacKay, Jenny Pickworth, J. H. Robertson, Clara Brink Shoemaker, J. G. White, R. J. Prosen and K. N. Trueblood Proceedings of the Royal Society of London. Series A, Mathematical and Physical Sciences Vol. 242, No. 1229 (Oct. 29, 1957), pp. 228-263 https://www.jstor.org/stable/100311
• Vitamin B12 Sources and Bioavailability Fumio Watanabe Experimental Biology and Medicine Volume 232, Issue 10 https://doi.org/10.3181/0703-MR-67