Enterohepatic circulation vitamin

Approximately 0.05 to 0.2% of vitamin > 2 stores are turned over daily, amounting to 0.5—8.0 )J.g, depending on the body pool size. The half-life of the body pool is estimated to be between 480 and 1360 days with a daily loss of vitamin > 2 of about 1 )J.g. Consequentiy, the daily minimum requirement for vitamin B22 is 1 fig. Three micrograms (3.0 J.g) vitamin B22 are excreted in the bile each day, but an efficient enterohepatic circulation salvages the vitamin from the bile and other intestinal secretions. This effective recycling of the vitamin contributes to the long half-life. Absence of the intrinsic factor intermpts the enterohepatic circulation. Vitamin > 2 is not catabolized by the body and is, therefore, excreted unchanged. About one-half of the vitamin is excreted in the urine and the other half in the bile. 

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

Pharmacokinetics The parietal cells of the stomach secrete intrinsic factor, which regulates the amount of vitamin B-12 absorbed in the terminal ileum. Bioavailability of oral preparations is approximately 25%. Vitamin B12 is primarily stored in the liver. Enterohepatic circulation plays a key role in recycling vitamin B-12 from mainly bile. If plasma-binding proteins are saturated, excess free vitamin B- 2 will be excreted in the kidney. 

Another possible mechanism involves the effect of saponins on micelle formation. Saponins are known to alter the size or shape of micelles (Oakenfull, 1986 Oakenfull and Sidhu, 1983), an observation that is consistent with decreased bile acid absorption (Stark and Madar, 1993) and increased fecal bile acid excretion (Malinow et al., 1981 Nakamura et al.,1999). Saponins may also directly bind bile acids (Oakenfull and Sidhu, 1989), which would presumably interfere with micelle formation and decrease cholesterol absorption. Other studies have found that saponins decrease the absorption of fat-soluble vitamins (Jenkins and Atwal, 1994) and triglycerides (Han et al., 2002 Okuda and Han, 2001), indicating decreased micelle formation. However, direct evidence showing impaired micelle formation in vivo is lacking. Moreover, Harwood et al. (1993) reported no change in bile acid absorption or interruption of the enterohepatic circulation of bile acids in hamsters fed tiqueside, despite significant reductions in cholesterol absorption. 

For some drugs that, for physiological and anatomical reasons, mainly follow a passive absorption mechanism, a satisfactory colonic absorption was demonstrated. Similar absorption rates from the small and large intestine were found for oxprenolol, metoprolol, isosorbide-5-mononitrate, and glibenclamide [9], It has also been known for many years, that some lipophilic vitamins, as well as bile salts and some steroids, that undergo enterohepatic circulation show satisfactory colonic absorption [2],... 

Figure 28-4. The enterohepatic circulation of vitamin B12. TCII (transcobalamin ID is the transport protein that carries newly absorbed dietary vitamin B12 from the intestine to tissues. Approximately 20% of circulating vitamin B12 is transported by TCII the remainder of vitamin B12 is bound toTCI.THF, tetrahydrofolate.

A further problem with studies in patients maintained on long-term total parenteral nutrition is that they are not normal healthy subjects - there is some good medical reason for their treatment Furthermore, they will have little or no enterohepatic recirculation of vitamins, and hence may have considerably higher requirements than normal there is considerable enterohepatic circulation of folate (Section 10.2.1) and vitamin B12 (Section 10.7.1). 

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. 

Estimates of requirements based on parenteral administration to subjects with pernicious anemia as a result of the lack of intrinsic factor (Section 10.9.2) are almost certainly erroneously high for subjects with normal enterohepatic circulation of the vitamin in pernicious anemia, the biliary vitamin B12 will not be reabsorbed to any significant extent, and requirements will therefore be considerably higher than normal. 

The daily loss is about 0.1% of the body pool in subjects with normal intrinsic factor secretion and enterohepatic circulation of the vitamin (Section 10.7.2). On this basis, the requirement is 0.3 to 1.8 nmol (1 to 2.5 /xg) per day (Herbert, 1987b). This is probably a considerable overestimate of requirements, because parenteral administration of less than 0.3 nmol per day is adequate to maintain normal hematology in patients with pernicious anemia, in whom the enterohepatic recycling of the vitamin is grossly impaired. 

The daily loss is about 0.1% of the body pool in subjects with normal intrinsic factor secretion turd enterohepatic circulation of the vitamin (Section... 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

Humans are efficient recyclers of vitamin Bi2 because of enterohepatic circulation. The vitamin is secreted in the bile. Upon combining with intrinsic factor, the absorption process is repeated. This recirculation probably explains why dietary deficiencies are uncommon and why the inability to produce intrinsic factor results in vitamin deficiency, even though there may be adequate dietary intake. 

Cholesterol is utilized in formation of membranes (Chapter 10), steroid hormones (Chapters 30,32, and 34), and bile acids. 7-Dehydrocholesterol is required for production of vitamin D (Chapter 37). Under steady-state conditions, the cholesterol content of the body is maintained relatively constant by balancing synthesis and dietary intake with utilization. The major consumer of cholesterol is formation of bile acids, of which about 0.8-1 g/day are produced in the liver and lost in the feces. However, secretion of bile acids by the liver is many times greater (15-20 g/day) than the rate of synthesis because of their enterohepatic circulation (Chapter 12). Cholesterol is also secreted into bile, and some is lost in feces as cholesterol and as coprostanol, a bacterial reduction product (about 0.4-0.5 g/day). Conversion of cholesterol to steroid hormones and of 7-dehydrocholesterol to vitamin D and elimination of their inactive metabolites, are of minor significance in the disposition of cholesterol, amounting to approximately 50 mg/day. A small amount of cholesterol... 

The major excretory route for vitamin D is bile. Vitamin D metabolites may undergo conjugation in the liver prior to secretion. An enterohepatic circulation of 25-(OH)D,... 

Vitamin B12 is stable to temperatures up to 250°C (482°F) in acidic or neutral solutions. Dietary B12 deficiency is rare among meat eaters but not in strict vegetarians. The average total body content of vitamin B12 is about 2.5 mg, most of which is in the liver (1 /u,g of Bi2 per gram of hepatic tissue). There is extensive reutilization of cobalamin and an active enterohepatic circulation. The principal disease caused by vitamin B12 deficiency is megaloblastic anemia. Deficiency also causes neurological abnormalities that become irreversible if allowed to persist. 

The importance and completeness of the enterohepatic circulation are demonstrated by strict vegetarians who consume no vitamin B12. They require 20-30 years or more to develop vitamin B12... 

The bile salts are syhthesized in the liver, stored ih the gallbladder, and released into the small intestine, where they emulsify dietary lipids and fat-soluble vitamins. This solubilization promotes the absorption of these dietary compounds through the intestinal mucosa. Bile salts are predominantly reabsorbed through the enterohepatic circulation and returned to the liver, where they exert a negative feedback control on 7a-hydroxylase and, thus, regulate any subsequent conversion of cholesterol (4,7). 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

There is a considerable enterohepatic circulation of vitamin B - Vitamin B and its metabolites (some of which are biologically inactive) are transferred from peripheral tissues to the liver bound to transcobalamin III. They are then secreted into the bile, bound to cobalophilins 3-8 Ig (2.25-6 nmol) of vitamin B may be secreted in the... 

Most estimates of vitamin B requirements are based on the amounts given parenterally to maintain normal health in patients with pernicious anaemia due to a failure of vitamin B absorption. This overestimates normal requirements because of the enterohepatic circulation of vitamin B (section 11.10.1) in people with defective absorption, the vitamin that is excreted in the bile will be lost in the faeces, whereas normally it is almost completely reabsorbed. 

The total body pool of vitamin is of the order of 2.5 mg (1.8 Jmol), with a minimum desirable body pool of about 1 mg (0.3 J.mol). The daily loss is about 0.1% of the body pool in subjects with normal enterohepatic circulation of the vitamin on this basis requirements are about 1-2.5 Jg/day, and reference intakes for adults range between 1.4 and 2.0 Jg. 

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