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 B
12 in what is an intricate and necessary mechanism to protect this vitamin from the acidic environment of the stomach.
Vitamin B
12 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 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
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 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
The pylorus ( or ), or pyloric part, connects the stomach to the duodenum. The pylorus is considered as having two parts, the ''pyloric antrum'' (opening to the body of the stomach) and the ''pyloric canal'' (opening to the duodenum). The ''pylori ...
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 protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
(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 B
12 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 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 final 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 posterior intestine or distal intestine ma ...
. The ileum is the longest of all portions of the small intestine, and has on its surface specialized receptors called
cubilin
Cubilin is a protein that in humans is encoded by the ''CUBN'' gene.
Function
Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a re ...
receptors, that identify the B
12–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 B
12 while it moves through the stomach.
Haptocorrin also circulates and binds approximately 80% of circulating B
12, 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
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{{refend
Digestive system