Vitamin B12 Lecture Biochemistry Prof.Dr.Hussein Al-Hakeim, فيتامين بي 12-كيمياء حياتية

Cobalamin (vitamin B12)
• Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center.



• Vitamin B12 from food bind to salivary transcobalamin I (Haptocorrin). Vitamin B12 is acid-sensitive and in binding to transcobalamin I it can safely pass through the acidic stomach to the duodenum. In the less acidic environment of the small intestine, pancreatic enzymes digest the transcobalamin I and vitamin B12 can then bind to intrinsic factor. This new complex is then absorbed by the intestinal cells the ileum. Inside the cells, vitamin B12 dissociates once again and binds to another protein, transcobalamin II; the new complex can then exit the epithelial cells to be carried to the liver.

##There are only two clinically significant reactions in the body that require vitamin B12 as a cofactor:1-. methylmalonyl-CoA mutase, 2- methionine synthase.
Clinical Significances of B12 Deficiency
1. The liver can store up to six years worth of vitamin B12, hence deficiencies in this vitamin are rare. Also the increase in Vitamin B12 in blood means there is a damage to the liver.
2. Pernicious anemia: is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. The anemia results from impaired DNA synthesis due to a block in purine and thymidine biosynthesis. The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism. When vitamin B12 is deficient essentially all of the folate becomes trapped as the N5-methylTHF derivative as a result of the loss of functional methionine synthase. This trapping prevents the synthesis of other N5,N10-THF required for the purine and thymidine nucleotide biosynthesis pathways that required required for the synthesis of DNA. Inhibition of DNA replication in red blood cells results in the formation of large, fragile megaloblastic red blood cells