# Haptocorrin

Haptocorrin (HC) also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalamin protein that in humans is encoded by the TCN1 gene. One essential function of haptocorrin is protection of the acid-sensitive vitamin B$_{12}$ while it moves through the stomach. A second function is serum HC binding of the great majority of circulating vitamin B$_{12}$, rendering it unavailable for take-up by cells. This is conjectured to be a circulating storage function.

## Functions

Haptocorrin (HC), also commonly known as the R-protein, or the R-factor, or previously referred to as transcobalamin I, is a unique glycoprotein produced by the salivary glands of the oral cavity, in response to ingestion of food. This protein binds strongly to vitamin B$_{12}$ in what is an intricate and necessary mechanism to protect this vitamin from the acidic environment of the stomach.$^{:44}$ Vitamin B$_{12}$ is an essential water-soluble vitamin, the deficiency of which creates anemia (macrocytic anemia), decreased bone marrow cell production (anemia, pancytopenia), neurological problems, as well as metabolic issues (methylmalonyl-CoA acidosis).$^{:50–51}$
Vitamin B$_{12}$ is therefore an important vitamin for the body to absorb. Despite its vital role however, vitamin B$_{12}$ is structurally very sensitive to the hydrochloric acid found in the stomach secretions, and easily denatures in that environment before it has a chance to be absorbed by the small intestine. Found in fresh animal products (such as liver), vitamin B$_{12}$ attaches haptocorrin, which has a high affinity for its molecular structure. Coupled together vitamin B$_{12}$ and haptocorrin create a complex. This haptocorrin–B$_{12}$ complex is impervious to the insult of the stomach acid, and passes on via the pylorus to the duodenum. In the duodenum pancreatic proteases (a component of pancreatic juice) cleave haptocorrin, releasing vitamin B$_{12}$ in its free form.
The same cells in the stomach that produce gastric hydrochloric acid, the parietal cells, also produce a molecule called the intrinsic factor (IF), which binds the B$_{12}$ after its release from haptocorrin by digestion, and without which only 1% of vitamin B$_{12}$ is absorbed. Intrinsic factor (IF) is a glycoprotein, with a molecular weight of 45 kDa. In the duodenum, the free vitamin B$_{12}$ attaches to the intrinsic factor (IF) to create a vitamin B$_{12}$–IF complex. This complex then travels through the small bowel and reaches the terminal tertiary portion of the small intestine, called the ileum. The ileum is the longest of all portions of the small intestine, and has on its surface specialized receptors called cubilin receptors, that identify the B$_{12}$–IF complexes and take them up into the circulation via endocytosis-mediated absorption.
Separate from the digestive absorption function, serum HC binds 80-90% of circulating B$_{12}$, rendering it unavailable for cellular delivery by transcobalamin II. This is conjectured to be a circulating storage function. Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B$_{12}$ while at the same time manifesting as a vitamin deficiency because of insufficient vitamin bound to transcobalamin II.