haptocorrin
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Haptocorrin also known as transcobalamin-1 (TC-1) or cobalophilin is a
transcobalamin Transcobalamins are carrier proteins which bind cobalamin (B12). Types * Transcobalamin I (TCN1), also known as haptocorrin, R-factor, and R-protein, is a glycoprotein produced by the salivary glands of the mouth. It primarily serves to protect ...
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach.


Function

Haptocorrin (HC), also commonly known as the R-protein, or the R-factor, or previously referred to as transcobalamin I, is a unique
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
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. Vitamin B12 is an essential water-soluble vitamin, the deficiency of which creates anemia (
macrocytic anemia The term ''macrocytic'' is from Greek words meaning "large cell". A macrocytic class of anemia is an ''anemia'' (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their no ...
), decreased bone marrow cell production (
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
,
pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood coun ...
), neurological problems, as well as metabolic issues ( methylmalonyl-CoA acidosis). 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 Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...
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. 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 The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
. In the duodenum pancreatic proteases (a component of
pancreatic juice Pancreatic juice is a liquid secreted by the pancreas, which contains a number of digestive enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, nucleases and amylase. The pancreas is located in the v ...
) cleave haptocorrin, releasing vitamin B12 in its free form. The same cells in the stomach that produce gastric hydrochloric acid, the
parietal cells Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the ...
, also produce a molecule called the
intrinsic factor Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption o ...
(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 Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
-mediated absorption. In short, the essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach. Haptocorrin also circulates and binds approximately 80% of circulating B12, rendering it unavailable for cellular delivery by
transcobalamin II Transcobalamins are carrier proteins which bind cobalamin (B12). Types * Transcobalamin I (TCN1), also known as haptocorrin, R-factor, and R-protein, is a glycoprotein produced by the salivary glands of the mouth. It primarily serves to protect ...
.


References


Further reading

* * * * * * * * * * * * * * * * * * * * {{refend Digestive system