Transcobalamin

Transcobalamin (TC) is a protein that plays a crucial role in the transport and delivery of vitamin B12 (cobalamin) within the body. It is a glycoprotein that is primarily synthesized in the liver and secreted into the bloodstream. Transcobalamin binds to vitamin B12 and facilitates its transport from the intestines, where it is absorbed, to various tissues and cells throughout the body.

Structure and Function

Transcobalamin is a large protein consisting of 432 amino acids. It is encoded by the TCN2 gene located on chromosome 22q12.2. The protein is synthesized as a precursor molecule, which undergoes post-translational modifications to form the mature active form of transcobalamin.

The main function of transcobalamin is to bind to vitamin B12 and protect it from degradation in the bloodstream. It acts as a carrier protein, ensuring that vitamin B12 is safely transported to its target tissues. Transcobalamin binds to vitamin B12 with high affinity, forming a stable complex that prevents its loss through filtration in the kidneys.

Role in Vitamin B12 Metabolism

Vitamin B12 is an essential nutrient that is required for various biological processes, including DNA synthesis, red blood cell production, and nerve function. However, vitamin B12 cannot be synthesized by the human body and must be obtained from dietary sources such as meat, fish, and dairy products.

After ingestion, vitamin B12 is released from food proteins in the stomach and binds to a protein called intrinsic factor (IF), which is secreted by the gastric parietal cells. The vitamin B12-IF complex then moves to the small intestine, where it is recognized by specific receptors on the surface of enterocytes. Transcobalamin, present in the intestinal mucosa, binds to the vitamin B12-IF complex and facilitates its uptake into the enterocytes.

Once inside the enterocytes, vitamin B12 is released from transcobalamin and binds to another protein called transcobalamin II (TCII). Transcobalamin II is responsible for transporting vitamin B12 across the intestinal epithelium and into the bloodstream. The vitamin B12-TCII complex is then released into the circulation, where it can be taken up by various tissues and cells.

Clinical Significance

Deficiencies in transcobalamin can lead to impaired vitamin B12 transport and subsequent deficiency. This can result in a condition known as megaloblastic anemia, characterized by the production of abnormally large red blood cells. Other symptoms of vitamin B12 deficiency include fatigue, weakness, neurological problems, and gastrointestinal disturbances.

Transcobalamin deficiency can be caused by genetic mutations in the TCN2 gene or by certain medical conditions that affect the liver's ability to produce the protein. Treatment typically involves vitamin B12 supplementation, either through oral or intramuscular administration, to bypass the need for transcobalamin-mediated transport.

References

1. Quadros EV. Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol. 2010;148(2):195-204. doi:10.1111/j.1365-2141.2009.07952.x 2. Lildballe DL, Mutti E, Birgens HS, Nexo E. Transcobalamin deficiency due to activation of an intra exonic cryptic splice site. Blood Cells Mol Dis. 2012;48(3):179-183. doi:10.1016/j.bcmd.2012.01.003