Vitamins, large

Another name for vitamin A is retinol, and its chemical structure contains a molecule with many unsaturated C=C bonds and also a CH2OH alcohol group. It is a fat-soluble vitamin. Large doses of vitamin A have been linked to some birth defects so many pregnant women are advised to avoid food supplements rich in vitamin A. 

Pharmacological dose of a vitamin. Large amounts of a vitamin, exceeding normal needs of the body. 

I6I C. Warfarin baits need contain only 0 025% active principle, and rats are killed after ingesting about 5 doses the bait can be left down and the risk of acute toxicity to man or domestic animals is not serious. In common with other coumarin derivatives, warfarin reduces the clotting power of blood and death is caused by haemorrhages initiated by any slight injury. Warfarin is a vitamin K antagonist, and large oral doses of the vitamin can be given as an antidote. 

A large number of selenium derivatives such as the selenium analog of vitamin B] have been tested for physiological activity (91). 

Some vitamin K is provided m the normal diet but a large proportion of that required by humans is produced by their intestinal flora... 

Fine chemical companies are generally either small and privately held or divisions of larger companies, such as Eastman Fine Chemicals (United States) and Lonza (Switzerland). Examples of large public fife science companies, which market fine chemicals as a subsidiary activity to their production for captive use, are Hoffmann-La Roche, Sandoz, and Boehringer Ingelheim, which produce and market bulk vitamins and liquid crystal intermediates, dyestuff intermediates, and bulk active ingredients, respectively. Table 3 fists some representative companies having an important fine chemical business. 

The antagonisms that exist between unsaturated fatty acids, and carotene and vitamin E are compHcated and largely undefined. Linoleic acid acts as an antivitamin to i7/-a-tocopherol [59-02-9, 1406-18-9, 10191-41-0] (vitamin E) by reducing availabiHty through direct intestinal destmction. Various Hpoxidases destroy carotenes and vitamin A (73). Dicoumarol [66-76-2] (3,3 -methylenebis(4-hydroxycoumarin)) is a tme antimetaboHte of vitamin K [12001 -79-5] but seems to occur only in clover and related materials that are used primarily as animal feeds (74). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The American Dietetic Association, the American Heart Association, and the National Heart, Lung and Blood Institute recommend 142—198 g (5—7 02) of lean, trimmed meat daily. It was also pointed out that trimmed meat, especially red meat, provides large amounts of essential nutrients such as iron, 2inc, vitamin balanced protein. The idea that the risk of CHD and cancer can be greatiy reduced by avoiding a meat-centered diet have prompted... 

A considerable quantity of oil can be extracted from waste material from shelling and processing plants, eg, the inedible kernels rejected during shelling and fragments of kernels recovered from shells. About 300 t of pecan oil and 300—600 t of English walnut oil are produced aimuaHy from such sources. The oil is refined and used for edible purposes or for the production of soap the cake is used in animal feeds (see Feeds and feed additives). Fmit-pit oils, which closely resemble and are often substituted for almond oil, are produced on a large scale for cosmetic and pharmaceutical purposes (143). For instance, leaves, bark, and pericarp of walnut may be used to manufacture vitamin C, medicines, dyes and tannin materials (144). 

The age pigments (lipofuscin), which accumulate with age, aie largely made up of these precipitated Hpid-proteia complexes resultiag from such cross-linking. Vitamin E may function to help prevent formation of these complexes. The metaboHc role of antioxidants (qv) such as vitamin E in animal tissues, however, remains quite controversial. 

Petrochemical-based methods of citral manufacture are very important for the large-scale manufacture of Vitamin A and carotenoids. Dehydrolinalool and its acetate are both made from the important intermediate, P-methyUieptenone. 

The production of a- and P-ionone ia the United States ia 1993 was about 120 t at an average price of 26.48/kg (67). a-Ionone is more valuable than P-ionone ia perfumery and sells for an average price of 30.41 /kg. P-Ionone is produced ia large volumes and production figures are not available. It is used mainly as an iatermediate for produciag Vitamin A. Production figures for methylionones are not available but they are much larger than the a- and P-ionones used for perfumery. 

The first commercial synthesis of a vitamin occurred ia 1933 when the Reichsteia approach was employed to manufacture vitamin C (6). AH 13 vitamins ate available ia commercial quantities, and their biological functions have largely been estabUshed (7). A Hst of Nobel prize winners associated with vitamin research is given ia Table 2. 

Reichsteia and Grbssner s second L-ascorbic acid synthesis became the basis for the iadustrial vitamin C production. Many chemical and technical modifications have improved the efficiency of each step, enabling this multistep synthesis to remain the principal, most economical process up to the present (ca 1997) (46). L-Ascorbic acid is produced ia large, iategrated, automated faciUties, involving both continuous and batch operations. The process steps are outlined ia Figure 7. Procedures require ca 1.7-kg L-sorbose/kg of L-ascorbic acid with ca 66% overall yield ia 1977 (55). Siace 1977, further continuous improvement of each vitamin C production step has taken place. Today s overall ascorbic acid yield from L-sorbose is ca 75%. In the mid-1930s, the overall yield from L-sorbose was ca 30%. 

Because of the time and expense involved, biological assays are used primarily for research purposes. The first chemical method for assaying L-ascorbic acid was the titration with 2,6-dichlorophenolindophenol solution (76). This method is not appHcable in the presence of a variety of interfering substances, eg, reduced metal ions, sulfites, tannins, or colored dyes. This 2,6-dichlorophenolindophenol method and other chemical and physiochemical methods are based on the reducing character of L-ascorbic acid (77). Colorimetric reactions with metal ions as weU as other redox systems, eg, potassium hexacyanoferrate(III), methylene blue, chloramine, etc, have been used for the assay, but they are unspecific because of interferences from a large number of reducing substances contained in foods and natural products (78). These methods have been used extensively in fish research (79). A specific photometric method for the assay of vitamin C in biological samples is based on the oxidation of ascorbic acid to dehydroascorbic acid with 2,4-dinitrophenylhydrazine (80). In the microfluorometric method, ascorbic acid is oxidized to dehydroascorbic acid in the presence of charcoal. The oxidized form is reacted with o-phenylenediamine to produce a fluorescent compound that is detected with an excitation maximum of ca 350 nm and an emission maximum of ca 430 nm (81). 

Vitamin Deficiency. Vitamin deficiency is uncommon in normal adults. However, when it does occur, it can be serious, particularly in pregnant women. Some vitamin deficiency can occur because of a large reduction of fat intake, which decreases absorption. Strict vegetarians also risk reduced vitamin intake. Premature infants and elderly people who are exposed to minimal sunlight and consume Htde vitamin also have a reduced capacity to metabolize and can develop vitamin deficiency. 

Although the industrial synthesis of vitamin remains largely unchanged from its early beginnings, significant effort has been devoted to improvements in the condensation step, the oxidation of dihydrovitarnin to vitamin K, and in economical approaches to vitamin (vide infra). Also, several chemical and biochemical alternatives to vitamin have been developed. 

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