Small intestine intrinsic factor

Food vitamin B 2 appears to bind to a saUvary transport protein referred to as the R-protein, R-binder, or haptocorrin. In the stomach, R-protein and the intrinsic factor competitively bind the vitamin. Release from the R-protein occurs in the small intestine by the action of pancreatic proteases, leading to specific binding to the intrinsic factor. The resultant complex is transported to the ileum where it is bound to a cell surface receptor and enters the intestinal cell. The vitamin is then freed from the intrinsic factor and bound to transcobalamin II in the enterocyte. The resulting complex enters the portal circulation. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Intrinsic factor is produced by the parietal cells. Within the stomach, it combines with vitamin Bu to form a complex necessary for absorption of this vitamin in the ileum of the small intestine. Vitamin B12 is an essential factor in the formation of red blood cells. Individuals unable to produce intrinsic factor cannot absorb vitamin B12 and red blood cell production is impaired. This condition, referred to as Pernicious anemia, occurs as a result of an autoimmune disorder involving destruction of parietal cells. 

Very small amounts of cobalamin are required each day (<5 i.g) and the diet normally provides plenty more than the minimum, so dietary B12 deficiency is uncommon, except in very strict vegetarians. Pernicious anaemia arises when a defect in the stomach results in too little secretion of a protein called intrinsic factor, without which, cobalamin cannot be absorbed in the ileum of the small intestine. 

There are several steps in the absorption of vitamin B. In the stomach and lumen of the small intestine it is hydrolysed from its (peptide) links with the proteins of which it is a component. It then attaches to gastric intrinsic factor, which is a glycoprotein of molecular mass about 50 000 kDa, to form a complex. This protects the vitamin from being damaged by acid in the stomach. The complex is carried into the ileum, where it binds to a receptor on the surface of the absorptive cells and is released from the intrinsic factor within the absorptive cell, hi the portal venous blood, it is transported to the liver bound to the vitamin B 12-binding protein, which also protects the vitamin. 

Cobalamine can only be resorbed in the small intestine when the gastric mucosa secretes what is known as intrinsic factor—a glycoprotein that binds cobalamine (the extrinsic factor) and thereby protects it from degradation. In the blood, the vitamin is bound to a special protein known as trans-cobalamin. The liver is able to store vitamin Bi2 in amounts suf cient to last for several months. Vitamin B12 deficiency is usually due to an absence of intrinsic factor and the resulting resorption disturbance. This leads to a disturbance in blood formation known as pernicious anemia. 

Vitamin B12. Vitamin B12 is a larger molecule than the other vitamins, and it can be absorbed via the intestine, which involves binding to specialized transport proteins.44 After oral administration, vitamin B12 binds to intrinsic factor (IF) produced from the parietal cells in the stomach and proximal cells in the duodenum. The vitamin B12—IF complex passes down the small intestine until it reaches the ileum, where the complex binds to a specific IF receptor located on the apical membrane of the villous enterocyte. The complex is then internalized via RME, vitamin B12 is released from IF by the action of cathepsin L on IF, and free vitamin B12 consequently forms the complex with transcobal-amin II to be delivered into the basolateral side of the membrane via the transcytotic pathway. 

Absorption of vitamin B12 takes place in the small intestine. It must be bound to the intrinsic factor to be absorbed in any quantity. 

Folic acid is involved in DNA synthesis and is needed to form three of the four bases of DNA. It is absorbed in the upper small intestine, but this does not require intrinsic factor. Folate deficiency may occur in alcoholics and other chronically malnourished people. 

Absorption of vitamin B12 can be investigated in several ways after oral delivery of radioactive vitamin B12 (e.g. containing Co) and subsequent measurement of radioactivity in faecal excretion, whole body counting or liver uptake, plasma radioactivity or the popular Schilling test. For the Schilling test, urinary excretion of radioactive vitamin B12 is measured 24 h following oral delivery, and impaired absorption may indicate intrinsic factor deficiency bacterial colonization of the small intestine (stagnant gut syndrome) or ileal disease. 

A-43 Vitamin B12 is not found in plant foods. The main source of B12 in human diet is through animal products like milk, eggs and liver. Vitamin B12 requires the presence of intrinsic factor from the stomach in order to be absorbed in the small intestines. The liver can store up to six years worth of vitamin B-12, hence deficiencies in this vitamin are rare. 

Vitamin B12 deficiency can occur due to lack of intrinsic factor, which is produced in the stomach and is essential for absorption of vitamin B12 after gastrectomy or because of impaired absorption due to disease of the small intestine. 

Pernicious anemia arises from a B12 deficiency. Gastric tissue secretes a glycoprotein called intrinsic factor, which complexes with ingested B12 in the digestive tract and promotes its absorption through the small intestine into the blood stream. Pernicious anemia results from insufficient secretion of intrinsic factor. Figure 20.22 outlines a probable explanation for why failure to absorb B12 leads to the deficiency of red blood cells that define anemias. 

Water-soluble vitamins are believed to be absorbed both by simple diffusion and by carrier-mediated transport, which is sodium-dependent, dtamin 65 is absorbed by passive diffusion, mainly in the small intestine, and the amount absorbed is related linearly to the amount in the digesta.The importance of a carrier glycoprotein (intrinsic factor) for the absorption of vitamin B12 has already been stressed (see p. 98). 

Vitamin B12 is not abundantly contained in foods and is especially scarce in plant foods. To absorb this rare vitamin efficiently, the human body has an ingenious system. Dietary vitamin B12 binds to gastric intrinsic factor and is transported via a receptor present in the small intestine to the epithelial cells here it and is taken up in the circulation where it binds to transcobalamin II. The complex of transcobalamin II and B12 is then transported to the eells of target organs by endocytosis via a receptor expressed in the membrane of the cells. 

Vitamin B12 deficiency results more commonly from a stomach defect than from a dietary deficiency. Before it can be absorbed the vitamin B12 (extrinsic factor) that is released from associated peptides and proteins in the stomach must combine with the intrinsic factor, a small glycoprotein secreted by the parietal cells. Subjects who suffer from pernicious anaemia fail to produce intrinsic factor with the result that the vitamin is not absorbed and must be given by injection. Vitamin B]2 produced by microbes in the lower reaches of the intestine is of no use to the body. 

---