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Cubam
Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum, specializing in absorption of vitamin B12. Cubam is essentially composed of amnionless (AMN), and cubilin. Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex. Clinical significance Vitamin B12 is an essential water-soluble vitamin, the absorption of which relies on a functional secretion of salivary haptocorrin, functional secretion of gastric intrinsic factor, functional cleavage of the haptocorrin via pancreatic protease, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsorption of vitamin B12, and subsequent macrocytic anemia. The most common cause of Vitamin B12 deficiency is deficiency of the intrinsic factor (IF) usually due to atrophic gastritis, which reduces ...
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Amnionless
Amnionless is a protein that in humans is encoded by the ''AMN'' gene. Function A complex of amnionless and cubilin forms the cubam receptor. The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. Clinical significance Mutations of the AMN gene may cause Imerslund–Gräsbeck syndrome Imerslund–Gräsbeck syndrome is a rare autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the "''Cubam''" receptor located in the terminal ileum. This receptor is composed of two proteins, amnionless (A ...
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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 restricted mode of expression according to protein profiling and transcriptomics analyses, and is essentially only present in the kidneys and small intestine. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. A complex of amnionless and cubilin forms the cubam receptor. Clinical significance Cubilin is a potential diagnostic and prognostic cancer biomarker for kidney cancer. Based on patient survival data, high levels of cubilin in tumor cells is a favourable prognostic biomarker in renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the mos ...
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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 may be used instead of ileum. Its main function is to absorb vitamin B12, bile salts, and whatever products of digestion that were not absorbed by the jejunum. The ileum follows the duodenum and jejunum and is separated from the cecum by the ileocecal valve (ICV). In humans, the ileum is about 2–4 m long, and the pH is usually between 7 and 8 (neutral or slightly basic). ''Ileum ''is derived from the Greek word ''eilein'', meaning "to twist up tightly". Structure The ileum is the third and final part of the small intestine. It follows the jejunum and ends at the ileocecal junction, where the terminal ileum communicates with the cecum of the large intestine through the ileocecal valve. The ileum, along with the jejunum, is susp ...
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Vitamin B12
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It is important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the circulatory system in the maturation of red blood cells in the bone marrow. Plants do not need cobalamin and carry out the reactions with enzymes that are not dependent on it. Vitamin B12 is the most chemically complex of all vitamins, and for humans, the only vitamin that must be sourced from animal-derived foods or from supplements. Only some archaea and bacteria can synthesize vitamin B12. Most people in developed countries get enough B12 from the consumption of meat or foods with animal sources. Foods containing vitamin B12 include meat, clams, liver, fish, poultry, eggs, and dairy products. Many breakfast cereals a ...
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Haptocorrin
Haptocorrin also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalamin protein that in humans is encoded by the gene. 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 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), decreased bone marrow cell production (anemia, pancytopenia), neurological problems, as well as metabolic issues ( methylmalonyl-CoA acidosis). Vitamin B12 is therefore an important vitamin for the body to absorb. Despite it ...
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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 of vitamin B12 later on in the distal ileum of the small intestine. In humans, the gastric intrinsic factor protein is encoded by the ''CBLIF'' gene. Haptocorrin ( transcobalamin I) is another glycoprotein secreted by the salivary glands which binds to vitamin B12. Vitamin B12 is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum. In the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B12 can then bind to intrinsic factor. This new complex is then absorbed by the epithelial cells ( enterocytes) of the ileum. Inside the cells, vitamin B12 dissociates once again and binds to another protein, transcobalamin II; the new ...
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Protease
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 formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism (breakdown of old proteins), and cell signaling. In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. Proteases can be found in all forms of life and viruses. They have independently evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms. Hierarchy of proteases Based on catalytic residue Proteases can be classified into seven broad groups: * Serine protea ...
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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 normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters (fL= 10−15 L). In metric terms the size is given in equivalent cubic micrometers (1 μm3 = 1 fL). The condition of having erythrocytes which (on average) are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal. In a macrocytic anemia, the larger red cells are always associated with insufficient ''numbers'' of cells and often also insufficient hemoglobin content per cell. Both of these factors work to the opposite effect of larger cell size, to finally result in a ''total blood hemoglobin concentration'' that is less than normal (i.e., anemia). Macrocytic anemia is not a disease in the sense o ...
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Atrophic Gastritis
Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency possibly leading to pernicious anemia; and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with '' Helicobacter pylori'', or can be autoimmune in origin. Those with autoimmune atrophic gastritis (''Type A gastritis'') are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria. Type A gastritis primarily affects the fundus (body) of the stomach and is more common with pernicious anemia. Type B gastritis primarily affects the antrum, and is more common with ''H. pylori'' infect ...
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Parietal Cell
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 stomach. They contain an extensive secretory network of canaliculi from which the HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a concentration gradient of about 3 million to 1, which is the steepest ion gradient formed in the human body. Parietal cells are primarily regulated via histamine, acetylcholine and gastrin signalling from both central and local modulators. Structure Canaliculus A canaliculus is an adaptation found on gastric parietal cells. It is a deep infolding, or little channel, which serves to increase the surface area, e.g. for secretion. The parietal cell membrane is dynamic; the numbers of canalic ...
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Pernicious Anemia
Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic factor needed for the absorption of vitamin B12. Anemia is defined as a condition in which the blood has a lower than normal amount of red blood cells or hemoglobin. There may be larger red blood cells than normal but they are not always present. The most common initial symptoms are tiredness, and weakness. Other signs and symptoms of anemia include breathlessness, dizziness, a sore red tongue, lightheadedness, headaches, poor ability to exercise, cold hands and feet, low blood pressure, pale or yellow skin, chest pain, and an irregular heartbeat. The digestive tract may also be disturbed giving symptoms that can include nausea and vomiting, heartburn, upset stomach and loss of appetite. Pernicious anemia can cause osteoporosis and m ...
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