Haptocorrin

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 B₁₂ in what is an intricate and necessary mechanism to protect this vitamin from the acidic environment of the stomach.^[4]: 44 Vitamin B₁₂ 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).^{[4]: 50–51}

Vitamin B₁₂ is therefore an important vitamin for the body to absorb. Despite its vital role however, vitamin B₁₂ 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 B₁₂ attaches haptocorrin, which has a high affinity for its molecular structure.^[5] Coupled together vitamin B₁₂ and haptocorrin create a complex. This haptocorrin–B₁₂ 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 B₁₂ 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 B₁₂ after its release from haptocorrin by digestion, and without which only 1% of vitamin B₁₂ is absorbed. Intrinsic factor (IF) is a glycoprotein, with a molecular weight of 45 kDa. In the duodenum, the free vitamin B₁₂ attaches to the intrinsic factor (IF) to create a vitamin B₁₂–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 B₁₂–IF complexes and take them up into the circulation via endocytosis-mediated absorption.^[6]

Separate from the digestive absorption function, serum HC binds 80-90% of circulating B₁₂, rendering it unavailable for cellular delivery by transcobalamin II. This is conjectured to be a circulating storage function.^[7] Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B₁₂ while at the same time manifesting as a vitamin deficiency because of insufficient vitamin bound to transcobalamin II.^[8]