Vitamin B12, is an essential water-soluble vitamin found in animal products (such as liver, meat, fish, and dairy products). Vitamin B12 is not found in plant sources; a vegetarian diet can be a risk factor for vitamin B12 deficiency. Normal daily intake of vitamin B12 is 7–30 micro gram, cooking has minimal effect on the structure of this vitamin. The minimal daily adult requirement is 1–3 micro gram, and the human body is able to store at any one time about 2–3 milligram, which is sufficient for at least 2 years of impeccable functioning before the source is depleted. In terms of absorption, no more than 2–3 microgram of vitamin B12 can be absorbed on a daily basis, with some 5–10 microgram of the vitamin B12 involved in enterohepatic circulation. This is in general a principal characteristic of water-soluble vitamins, in that no matter the oral intake, there is a certain threshold for intestinal absorption hence, low or non-existent chance of intoxication, as opposed to fat-soluble vitamins. Vitamin B12 has a major function in the nuclear replication of the DNA. It is therefore logical that its deficiency causes decrease bone marrow production, one of the most common manifestations of which is decreased red blood cell production or as it is referred to medically, anemia. Vitamin B12 however has two major forms in the human body: * Deoxyadenosyl B12 or as it is sometimes referred to Ado B12: Ado B12 is essential for acid-base maintenance of the blood, simply because Ado B12 is the catalyst that assists the conversion of methylmalonyl CoA into succinyl CoA. In absence of vitamin B12, levels of methylmalonyl CoA increase, and this is in fact a great way to distinguish folate deficiency macrocytic anemia, from vitamin B12 deficiency anemia. The following is the reaction in which Ado B12, plays a pivotal role: Propionyl CoA → Methylmalonyl CoA → Succinyl CoA * Methyl B12: This form of vitamin B12 is essential for conversion of Methy-THF (methyl tetrahydrofolate) into THF, and methyl (CH3). The methyl group is then used to add carbon, to homocysteine, converting it into methionine. Methionine is further converted to S-adenosyl methionine, which in turn gives of the extra carbon it received from THF, now to a DNA nucleotide, becoming S-adenosyl homocysteine. S-adenosyl Homocysteine, further loses its "S-adenosyl" attachment, to become homocysteine, and the cycle repeats yet again! Methyl THF → CH3 + THF ↓ Homocysteine → Methionine S-adenosyl ← ↑ ↓ ← S-adenosyl S-adenosyl Homocysteine ← S-adenosyl Methionine ↓ CH3 ↓ DNA → Methyl-DNA It is therefore understood that vitamin B12 is involved in complex DNA synthesis, along with folate, as well as in acid-base metabolism. To understand the basic pathophysiology of<unk> , it is imperative to understand the absorption of vitamin B12. The following lists principal events that lead to absorption of vitamin B12 along the GI tract: * Oral cavity: vitamin B12 containing food is ingested. Salivary glands produce haptocorrin, which binds vitamin B12, creating a "vitamin B12-Haptocorrin complex". This complex is then ingested via esophageal peristalsis into the stomach. * Stomach: vitamin B12-Haptocorrin, survives the low pH, highly osmotic environment of the stomach. Parietal cells produce hydrochloric acid (the effect of which Haptocorrin protects vitamin B12 from), and also intrinsic factor (IF). Intrinsic factor also has a high binding affinity for vitamin B12, but because that position is already filled by Haptocorrin, free intrinsic factor, and "Haptocorrin-vitamin B12" complex, empty from the stomach into the duodenum. * duodenum: Pancreatic juice, produced by the pancreas, contains pancreatic proteases that break the haptocorrin, degrading it and freeing the vitamin B12. Once free, vitamin B12, binds with intrinsic factor (IF), to produce an "IF-vitamin B12" complex. * Ileum: Cubam, a receptor found in the terminal portion of the ileum is a specialized receptor complex. The complex is responsible for the recognition of the "vitamin B12-IF" complex and initiating the endocytosis of the complex, resulting in absorption. Cubam is composed of two molecules, amnionless (AMN) and cubilin. Cubilin is a multi-ligand protein that contains eight epidermal growth factor (EGF) repeats and 27 CUB domains, from which the four active domains (CUB5-8) collectively get involved in binding interaction with the IF-Cbl complex. Whereas, amnionless is an apical transmembrane protein which is expressed in both intestine and kidney, and it seems to assist the subcellular localization and endocytosis of the cubilin by binding to its amino-terminal residues. Cubilin specializes in recognition of the "vitamin B12-IF" complex and attaches to it, while amnionless (AMN) is responsible for initiation of the endocytosis of complex and the subsequent absorption of vitamin B12. It is at this point that the pathology of IGS<unk>  occurs by preventing the absorption of vitamin B12, and can be caused by a mutation in either the amnionless (AMN) portion or the cubilin portion of the receptor.
Imerslund–Gräsbeck syndrome
Kohlschütter-Tönz syndrome
Naegeli–Franceschetti–Jadassohn syndrome
König's syndrome
Franceschetti–Klein syndrome
Parry–Romberg syndrome
Schöpf–Schulz–Passarge syndrome
Zechi-Ceide syndrome