Vitamin bacterial synthesis

The K vitamins include vitamin Ki, phylloquinone or phytonadione, and vitamin K2 which is a group of compounds, the menaquinones. Menadione, vitamin K3, is a precursor of menaquinone-4. Vitamin K is present in alfalfa and fish livers. Other dietary sources include green vegetables, soybean oil and eggs. A normal diet together with the bacterial synthesis of vitamin K in the gut are usually sufficient to prevent deficiencies in healthy adults. 

Vitamin K is found in cabbage, cauliflower, spinach, egg yolk, and liver. There is also extensive synthesis of the vitamin by the bacteria in the gut. There is no RDA for vitamin K, but 70 to 140 mg/day is recommended as an adequate level. The lower level assumes one half of the estimated requirement comes from bacterial synthesis, whereas the upper figure assumes no bacterial synthesis. 

Factors which cause a decrease in bioavailability include 111 high urinary excretion (2) destruction by certain mlesiinal bacteria (2) increased urinary excretion caused by vitamin C (4) presence of sulfonamides which block intestinal synthesis and (5) a decrease in absorption mechanisms. Increase in bioavailability can be provided by stimulating intestinal bacterial synthesis in certain species. No toxicity due to folic acid has been reported in humans. 

Ruminant animals obtain their B12 from bacterial synthesis that takes place in the rumen. As a result, these animals may suffer from vitamin B12 deficiency when they are grazed on cobalt-deficient pastures because the rumen bacteria will be unable to produce the vitamin. 

The vitamin B12 that occurs in nature is produced almost entirely by bacterial synthesis in animals but not in humans (Battersby, 1994). The richest dietary sources of vitamin B12 are organ meats, such as fiver and kidney. Lesser amounts are present in shellfish, chicken, fish, muscle meats, and dairy products (the principal source in lacto-vegetarians). Plants contain no vitamin B12 unless they are contaminated by bacteria, and foods that contain microorganisms often provide the only source of vitamin B12 for strict vegetarians, such as the vegans of southern India. 

The determination of vitamin K requirements is complicated by the intestinal bacterial synthesis of menaquinones and the extent to which these are absorbed and utilized (Section 5.1). Prolonged use of antibiotics leads to impaired blood clotting, but simple dietary restriction of vitamin K results in prolonged prothrombin time and increased circulating preprothrombin so it is apparent that bacterial synthesis is inadequate to meet requirements in the absence of a dietary intake of phylloquinone. Preprothrombin is elevated at intakes between 40 to 60 /xg per day, but not at intakes above 80 /rg per day (Suttie etal., 1988). 

Dietary deficiency is relatively widespread, yet is apparently never fatal there is not even a clearly characteristic riboflavin deficiency disease. In addition to intestinal bacterial synthesis of the vitamin, there is very efficient conservation and reutilization of riboflavin in tissues. Flavin coenzymes are tightly enzyme bound, in some cases covalently, and control of tissue flavins is largely at the level of synthesis and catabolism of flavin-dependent enzymes. 

Intestinal bacteria synthesize riboflavin, and fecal losses of the vitamin may be five- to six-fold higher than intake. It is possible that bacterial synthesis makes a significant contribution to riboflavin intake, because there is carrier-mediated uptake of riboflavin into colonocytes in culture. The activity of the carrier is increased in riboflavin deficiency and decreased when the cells are cultured in the presence of high concentrations of riboflavin. The same carrier mechanism seems to be involved in tissue uptake of riboflavin (Said et al., 2000). 

As a result of this resorption and the protein binding of plasma biotin, which reduces filtration at the glomerulus, renal clearance of biotin is only 40% of that of creatinine. This efficient conservation of biotin, together with the recycling of biocytin released from the catabolism of biotin-containing enzymes, may be as important as intestinal bacterial synthesis of the vitamin in explaining the rarity of deficiency. 

On the basis of studies in patients who developed deficiency during total parenteral nutrition, and who are therefore presumably wholly reliant on an exogenous source of the vitamin - with no significant contribution from intestinal bacterial synthesis - the provision of 60 fxg of biotin per day for adults receiving total parenteral nutrition is generally recommended (Bitsch et al., 1985). 

Alterations in gut flora by antimicrobials may potentiate oral anticoagulant by reducing bacterial synthesis of vitamin K (usually only after antimicrobials are given orally in high dose, e.g. to treat Helicobacter pylori). 

Animals depend on two. sources for their intake of this vitamin, dietary and bacterial synthesis. Table 26-7 lists ev cclicnt sources of vitamin K. ... 

The entire metabolic pathway of vitamin K has not been elucidated. The major urinary metabolites, however, are glu-curonidc conjugates of carboxylic acids derived from shortening of the side chain. High fecal concentrations are probably due to bacterial synthesis. 

Not fully understood. Sulfamethoxazole is a known inhibitor of the cytochrome P450 isoenzyme CYP2C9, by which S-warfarin in predominantly metabolised. The finding that co-trimoxazole caused a modest 22% increase in S-warfarin levels supports this mechanism. Acenocoumarol and phenprocoumon are also metabolised by CYP2C9 and might be expected to be similarly affected. Plasma protein binding displacement has been suggested as a mechanism, but on its own it does not provide an adequate explanation because the interaction is sustained. Sulfonamides can drastically reduce the intestinal bacterial synthesis of vitamin K, but this is not normally an essential source of the vitamin unless dietary sources are exceptionally low, see also Coumarins + Antibacterials , p.365. 

Vitamin K> (3-difamesylmenadione), as bacterial growth factor, VI, 208 bacterial synthesis of, VI, 208 biological conversion to menadione, VI, 34... 

Manganese and molybdenum are essential for enzymes in humans and other animals, but a dietary deficiency of these minerals is exceedingly rare in humans. Oobalt is essential for vitamin B12, but the human body cannot make vitamin B12 from cobalt and thus requires the preformed vitamin from dietary sources. (It is possible to derive some vitamin B12 from bacterial synthesis in the digestive tract.)... 

These studies show that germ-free existence is possible. In addition they throw fresh light on the question of intestinal synthesis of B vitamins, for the concentration of B vitamins in the gut does not necessarily imply bacterial synthesis. 

Intestinal bacteria synthesize a variety of menaquinones, which are absorbed to a limited extent from the large intestine, again into the lymphatic system, cleared by the liver and released in VLDL. It is often suggested that about half the requirement for vitamin K is met by intestinal bacterial synthesis, but there is little evidence for this, other than the fact that about half the vitamin K in liver is phylloquinone and the remainder a variety of menaquinones. It is not clear to what extent the menaquinones are biologically active — it is possible to induce signs of vitamin K deficiency simply be feeding a phylloquinone-deficient diet without inhibiting intestinal bacterial action. 

Man, monkeys, chicks, turkeys, fox, and mink must have folacin supplied in the food in order to avoid deficiency symptoms. Rats, dogs, rabbits, and pigs can meet their need for this vitamin through bacterial synthesis in the intestine. 

The establishment of allowances for vitamin B-6 is complicated by the following facts (1) the requirement varies with dietary protein intake—there is increased need for vitamin B-6 with increased intakes of protein (2) the uncertainty of the availability of the vitamin in the diet and (3) the uncertainty as to the extent of intestinal bacterial synthesis of the vitamin, and the degree to which it is utilized by the body. Also, there is evidence of increased need of the vitamin in pregnancy and lactation, in the elderly, and in various pathologic and genetic disturbances. Nevertheless, the NRC has set recommended allowances to assure a safety margin and to make a deficiency unlikely under most circumstances. Discussion follows ... 

Storage. Vitamin K is stored only in small amounts. Modest amounts are stored in the liver, with the skin and muscle following in concentration. About 50% of the vitamin K found in the human liver is K, from the diet the other 50% is K2 from bacterial synthesis in the intestine. 

Bacterial contamination of specimens must be avoided in view of the production of vitamin Bm by some organisms, and of its removal from solution by others. The activity of some urines stored at 4 C. has in fact been found to increase, presumably either from breakdown of previously inactive compounds or from bacterial synthesis. Addition of toluene has assisted in preservation but the volatile preservatives recommended by Hutner and Bjerknes (22) may be more suitable for this purpose, provided that 100 C. heating is carried out. Urine must be completely free from any contamination with feces because of its high content of vitamin Bi . 

The contribution of the gut flora to the available pantothenate for humans is unknown, but there is some evidence that bacterial synthesis of the vitamin may be important in animals, especially ruminants, since severe deficiency can only be achieved by using antibiotics or antagonists. Clinical conditions such as ulcers or colitis can adversely affect pantothenate status and excretion rates, and dietary fiber may affect its absorption. 

A completely independent study implicating the intestinal bacteria was that of Theiler and his associates (13) in ruminant animals. In the attempt to reproduce experimentally a South African paralytic disease known as lamzietke they fed cattle an experimental diet deficient in vitamin B and noted that evidences of deficiency failed to develop although pigeons on the same diet developed polyneuritis promptly. They assumed that either the vitamin requirement of cattle was extremely low or that it had been satisfied by bacterial synthesis in the intestinal tract the latter explanation seemed the more probable. 

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