Vitamin Releasing 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. 

The conjugation of vitamin B12 has been shown to increase oral bioavailability of peptides, proteins, and particles.44 46 62,63 Russsell-Jones and coworkers have attempted to exploit RME of vitamin B12 for the enhanced intestinal uptake of macromolecules such as luteinizing hormone—releasing factor (LHRH), granulocyte colony-stimulating factor, erythropoietin, and a-interferon.44,46,63 Also, they demonstrated that surface modification of nanoparticles with vitamin B12 can increase their intestinal uptake.44,62 The extended applications of this unique transport system, however, appear partially hampered by its limited uptake capacity. In human being, the uptake of vitamin B12 is only 1 nmol per intestinal passage. 

Considerably more intrinsic factor is secreted than is needed for the binding and absorption of dietary vitamin B12, which requires only about 1 % of the total intrinsic factor available. There is a considerable enterohepatic circulation of vitamin B12, variously estimated as between 1 to 9 /rg per day, about the same as the dietary intake. Like dietary vitamin B12 bound to salivary cobalophilin, the biliary cobalophUins are hydrolyzed in the duodenum, and the vitamin released binds to intrinsic factor, thus permitting reabsorption in the Ueum. Whereas cobalophUins and transcorrin III have low specificity, and wUl bind a variety of corrinoids, intrinsic factor orUy binds cobalamins, and only the biologicaUy active vitamin wiU be reabsorbed to any significant extent. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Many kinds of amino acids (eg, L-lysine, L-omithine, t-phenylalanine, L-threonine, L-tyrosine, L-valine) are accumulated by auxotrophic mutant strains (which are altered to require some growth factors such as vitamins and amino acids) (Table 6, Primary mutation) (22). In these mutants, the formation of regulatory effector(s) on the amino acid biosynthesis is genetically blocked and the concentration of the effector(s) is kept low enough to release the regulation and iaduce the overproduction of the corresponding amino acid and its accumulation outside the cells (22). 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

In the future, this test may be replaced by the proteins induced by vitamin K antagonists absence (PIVKA) concentrations in serum. PIVKAs are coagulation factor precursors, normally not detectable in blood but released into the... 

The a ns wer is a. (Hardman, pp 1525-1528.) Pa r a thyroid ho r m o ne is synthesized by and released from the parathyroid gland increased synthesis of PTI1 is a response to low serum Ca concentrations. Resorption and mobilization of Ca and phosphate from bone are increased in response to elevated PTI1 concentrations. Replacement of body stores of Ca is enhanced by the capacity of PTH to promote increased absorption of Ca by the small intestine in concert with vitamin D, which is the primary factor that enhances intestinal Ca absorption. Parathyroid hormone also causes an increased renal tubular reabsorption of Ca and excretion of phosphate. As a consequence of these effects, the extracellular Ca concentration becomes elevated. 

Warfarin and dicoumaroi antagonize the Y-carboxjdation activity of vitamin K atid thus act as anticoagulants. They interfere with the cotranslational modification during synthesis of the precoagulation factors. Once these proteins have been released into the bloodstream, vitamin K is no longer important for their subsequent activation and function. Itdated to this are two... 

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. 

A few substances are so large or impermeant that they can enter cells only by endocytosis, the process by which the substance is bound at a cell-surface receptor, engulfed by the cell membrane, and carried into the cell by pinching off of the newly formed vesicle inside the membrane. The substance can then be released inside the cytosol by breakdown of the vesicle membrane. Figure 1-5D. This process is responsible for the transport of vitamin B12, complexed with a binding protein (intrinsic factor) across the wall of the gut into the blood. Similarly, iron is transported into hemoglobin-synthesizing red blood cell precursors in association with the protein transferrin. Specific receptors for the transport proteins must be present for this process to work. 

Schindler R, Mentlein R. 2006. Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr 6 1477-1482. 

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. 

Very little work has been reported on the role of oxidative stress in osteoblasts. However, osteoblasts can be induced to produce intracellular ROS (Cortizo et al., 2000 Liu et al., 1999), which can cause a decrease in alkalinephosphatase (ALP) activity that is partially inhibited by vitamin E and cause cell death (Cortizo et al., 2000 Liu et al., 1999). Treatment of rat osteosarcoma ROS 17/2.8 cells with tumor necrosis factor-alpha (TNF-a) suppressed bone sialoprotein (BSP) gene transcription through a tyrosine kinase-dependent pathway that generates ROS (Samoto et al., 2002). H202 modulated intracellular calcium (Ca2+) activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores (Nam et al., 2002). 

In case LDL oxidation is considered as an important risk factor, the dosage of vitamin E may be important to determine a clinical effect. However, with respect to inhibition of protein kinase-C and the release of proinflammatory cytokines the intracellular transfer of RRRT (natural vitamin E) by the tocopherol-associated protein may be a crucial point. Consequently, natural vitamin E is considered more effective than the synthetic one. Since the activity on LDL oxidation was pointed out as important for the prevention of cardiovascular disease, most of the long-term trials with vitamin E were conducted at dosages >200 mg/day (about 200 lU/d). In a recent meta-analysis the association of plasma levels and mortality was studied in 1168 elderly European men and women (25). No association was found between the plasma concentration and all-cause or cause-specific mortality. 

Patients with exocrine pancreatic dysfunction may malabsorb vitamin B12 because a considerable part of the dietary vitamin may bind to R-proteins in the stomach. The R-proteins are normally broken down by pancreatic enzymes. The vitamin is released and binding to intrinsic factor then takes place. If the R-proteins are not degraded, then the vitamin B12 will remain bound to these proteins and will not be absorbed (M10). Harms and his colleagues (H27) measured vitamin B12 absorption in 19 children with exocrine pancreatic insufficiency and found the average absorption to be 8.0% compared to 59.2% in a control group. Adding pancreatin to the test dose of radiolabeled vitamin B12 increased absorption of the vitamin to an average of 61%. 

Attempts to demonstrate 25-hydroxy-vitamin D3-l-hydroxylase activity in vitro with rat kidney homogenates have been unsuccessful, although chick kidney preparations exhibit such activity. A heat-labile and very potent inhibitor of the hydroxylase has now been found in the rat preparation 322 all fractions of the kidney homogenate contained the factor, but the microsomes were the richest source, and they released the inhibitor during incubation. A similar inhibitor is also present in rat intestine and serum and in pig kidney, and it may well play a regulatory role in the synthesis of 1,25-dihydroxy-vitamin D3.323 Direct spectroscopic and inhibitory evidence for the presence of cytochrome P450 in kidney mitochondria and of its... 

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