Vitamin significance

In contrast to other water-soluble vitamins, significant amounts (4 to 5 mg) of vitamin B-i2 are stored in the body. As a result, it may fete several years tor the clinical symptoms of B12 deficiency to develop in individuals who have had a partial or total gastrectomy (/vhq therefore, become intrinsic factor-deficient) and can no longer absorb the vitamin. 

Toxicity. Thiamin from the diet is absorbed in the intestine by a carrier-mediated process (Rindi and Ventura, 1972). The process is saturable and is soditjm and energy-dependent. Therefore, because of this active carrier-mediated transport system, an oral intake of thiamin greater than 10 mg does not generally Increase blood levels of the vitamin significantly. The oral lethal dose for thiamin is above 2000 mg/kg for rodents. Parenteral administration of the vitamin is toxic (LD50), in the ranges from 80-120 mg/kg (iv) and 300-500 mg/kg (ip) for rodents (Cumming et al, 1980). 

Epidemiologic studies in Japan indicate an increased risk of stomach cancer owing to consumption of broiled fish and meats (116). In the United States, stomach cancer incidence has steadily declined since the 1940s, whereas consumption of broiled food has increased (108). In addition, the average human intake of PAHs is only 0.002 of that required to produce cancer in half of animals fed. Test results are often contradictory (117) and many components of food, such as vitamin A, unsaturated fatty acids, thiols, nitrites, and even saUva itself, tend to inhibit the mutagenic activity of PAHs (118—120). Therefore, the significance of PAHs in the human diet remains unknown (121,109). 

The i j -configuration of the 6,7-double bond in pre-vitamin D is critical to its subsequent thermal rearrangement to the active vitamin. A photochemical isomerization of pre-vitamin D to yield the inactive trans-isoTnen occurs under conditions of synthesis, and is especially detrimental if there is a significant short wavelength component, eg, 254 nm, to the radiation continuum used to effect the synthesis. This side reaction reduces overall yield of the process and limits conversion yields to ca 60% (71). Photochemical reconversion of the inactive side product, tachysterol, to pre-vitamin D allows recovery of the product which would otherwise be lost, and improves economics of the overall process (70). 

A number of studies have shown that vitamins moderate the induction of chromosomal aberrations by radiation. Vitamins C and E given orally to mice either 2 h before, immediately after, or 2 h after 1 Gy (100 rad) of y-ray TBI significantly reduce the frequencies of micronuclei and chromosomal aberrations in BM cells. Vitamin E is the more effective (95). Administration of vitamins C and E within 5 min of irradiation is as effective as pretreatment. Protection by vitamin C has also been shown in humans. Whereas chronic treatment of rats using vitamin C (100 or 300 mg/(kg/d)) for six months prior to TBI protects against chromosomal aberrations, vitamin E is not radioprotective in this setting (96). 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

Common names, chemical stmcture, and synonyms for the vitamins are given in Table 3. The names given to the vitamins and/or their letter designations do not foUow a logical pattern and are of historical significance only. Despite this, the nomenclature is in common use. 

The use of vitamins in humans consumes ca 40% of vitamins made worldwide. The majority of the vitamins, particularly in countries outside the United States, are used in animal husbandry. It is well estabUshed (21) that vitamins are critical to animal productivity, especially under confined, rapid growth conditions. Newer information (22) has shown that vitamin E added to catde feed has the additional effect of significantly prolonging beef shelf life in stores. Additional appHcations of vitamins exist. A small but growing market segment involves cosmetics (qv) (23). The use of the chemical properties of the vitamins, particularly as antioxidants (qv) in foods and, more recently, in plastics (vitamin E (24)), has emerged as a growing trend. 

Vitamins are sold for direct appHcation to foods and animal feeds. In addition, they are further processed into nutritional supplements. This last market is particularly significant in the United States. In many other countries, vitamins are regulated as dmgs, leading to a much lower supplement usage. 

It can be estimated that approximately 3,000,000,000 of vitamins were sold in 1996. Market growth is slightly higher than population growth, but varies widely by individual vitamin, geographical area, and/or appHcation. The largest vitamin manufacturer is Hoffmann-La Roche. Other significant producers include BASE, Takeda, Eisai, and Rhc ne-Poulenc. Additional vitamins are produced in China, Russia and India. 

The most significant chemical characteristic of L-ascorbic acid (1) is its oxidation to dehydro-L-ascorbic acid (L-// fi (9-2,3-hexodiulosonic acid y-lactone) (3) (Fig. 1). Vitamin C is a redox system containing at least three substances L-ascorbic acid, monodehydro-L-ascorbic acid, and dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid and the intermediate product of the oxidation, the monodehydro-L-ascorbic acid free radical (2), have antiscorbutic activity equal to L-ascorbic acid. 

Pyridine carboxamide [98-92-0] (nicotinamide) (1) and 3-pyridine carboxylic acid [59-67-6] (nicotinic acid) (2) have a rich history and their early significance stems not from their importance as a vitamin but rather as products derived from the oxidation of nicotine. In 1867, Huber prepared nicotinic acid from the potassium dichromate oxidation of nicotine. Many years later, Engler prepared nicotinamide. Workers at the turn of the twentieth century isolated nicotinic acid from several natural sources. In 1894, Su2uki isolated nicotinic acid from rice bran, and in 1912 Funk isolated the same substance from yeast (1). 

Significant additional progress will be necessary before cost-effective production of vitamin B by bioprocesses is possible. 

Vitamin A constitutes the most significant sector of the commercial retinoid market and is used primarily in the feed area. In the pharmaceutical area, there are several important therapeutic dermatologic agents which stmcturaHy resemble vitamin A and they are depicted in Figure 2 (see Pharmaceuticals). The carotenoids as provitamin A compounds also represent an important commercial class of compounds with P-carotene [7235-40-7] (10) occupying the central role (Fig. 3) (9). 

Vitamin A acetate [11098-51-4] (2) is the commercially significant form of the vitamin and is mainly produced by Hoffmann-La Roche, BASF, and Rhc ne-Poulenc (Fig. 4). AH of these processes have P ionone (18) as their key intermediate and in this regard are based on work performed in the 1940s... 

Fertile sources of carotenoids include carrots and leafy green vegetables such as spinach. Tomatoes contain significant amounts of the red carotenoid, lycopene. Although lycopene has no vitamin A activity, it is a particularly efficient antioxidant (see Antioxidants). Oxidation of carotenoids to biologically inactive xanthophyUs represents an important degradation pathway for these compounds (56). 

Aqueous solutions of vitamin > 2 at pH 4.0 to 7.0 show no decomposition during extended storage at 25°C. For optimum stability at elevated temperatures, solutions should be adjusted to pH 4.0 to 4.5. Aqueous solutions in this pH range maybe autoclaved for 20 min at 120°C without significant decomp o sition. 

The discovery that vitamin was metabolized to biologically active derivatives led to a significant effort to prepare 25-hydroxy vitamin and, subsequendy, the 1 a-hydroxy and 1,25 dihydroxy derivatives. Initial attempts centered around modification of steroidal precursors, which were then converted to the D derivatives by conventional means. 

Vitamin D deficiency in animals may be caused by the fact that the vitamin is not available to the hvestock. Modem animal husbandry subjects animals to total confinement with htde or no exposure to sunlight. This mandates that they be given vitamin D-fortified diets. The vitamin is sensitive to oxidation, heat, light, and minerals, and significant losses may occur in the fortified feed unless the product is adequately protected. Mycotoxins in feeds also interfere with utilization of vitamin D in feeds (207—209). 

Chromatographic methods including thin-layer, hplc, and gc methods have been developed. In addition to developments ia the types of columns and eluents for hplc appHcations, a significant amount of work has been done ia the kiads of detectioa methods for the vitamin. These detectioa methods iaclude direct detectioa by uv, fluoresceace after post-column reduction of the quiaone to the hydroquinone, and electrochemical detection. Quantitative gc methods have been developed for the vitamin but have found limited appHcations. However, gc methods coupled with highly sensitive detection methods such as gc/ms do represent a powerful analytical tool (20). 

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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