Vitamins, continued

Although a tremendous number of fermentation processes have been researched and developed to various extents, only a couple of hundred ate used commercially. Fermentation industries have continued to expand in terms of the number of new products on the market, the total volume (capacity), and the total sales value of the products. The early 1990s U.S. market for fermentation products was estimated to be in the 9-10 x 10 range. The total world market is probably three times that figure, and antibiotics continue to comprise a primary share of the industry. Other principal product categories are enzymes, several organic acids, baker s yeast, ethanol (qv), vitamins (qv), and steroid hormones (qv). 

There are numerous reports of the effects of antioxidant vitamins on transformation. Vitamin C suppresses x-ray-induced transformation when CSHlOTy cells are treated daily for one week following irradiation (97), suppresses transformation by y-rays or neutrons, and prevents the promotion of radiation-induced transformation by 12-0-tetradecanoylphorbol 13-acetate (TPA), but has no effect on cell survival (98). In these studies, the continuous presence of vitamin C for a critical period appears to be necessary for suppression of transformation. Vitamin C may act on the promotion stage of... 

More than one process is available for some of the vitamins. Further, manufacturers have developed variants of the classical syntheses during Optimization. Whereas some of this information is available, as described in the individual sections on vitamins, much is closely held as trade secrets. Judging from the more recent patent Hterature, the assessment can be made that vitamin production technologies are in general mature. However, the economic value of these products drives continuing research aimed at breakthrough processes. Annual production of vitamins varies gready, from ca 10 metric tons of vitamin B 2 to ca 50,000 metric tons of vitamin C. 

It is generally assumed that adequate vitamin levels in humans can be obtained through a balanced diet. However, ongoing studies continue to indicate that the majority of the U.S. population is not receiving even the RDA through diet. Supplementary vitamins are thus provided for fortification of foods (20) and as oral or parenteral dosage forms. 

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%. 

Market Forms. Vitamin B 2 is sold almost exclusively as cyanocobalamin. Approximately one-third of the material is for the human pharmaceutical market whereas two-thirds is used in the animal feed market, primarily for poultry and swine (see Feeds AND FEED ADDITIVES). Modest growth in both markets has occurred in the period 1980—1995 and this trend is expected to continue. 

More than 20 other, naturally occurring metaboUtes of vitamin D have been isolated and characterized, and many derivatives have been synthesized. Their function is the subject of continuing research (16,51,141,162). 

PTH has a dual effect on bone cells, depending on the temporal mode of administration given intermittently, PTH stimulates osteoblast activity and leads to substantial increases in bone density. In contrast, when given (or secreted) continuously, PTH stimulates osteoclast-mediated bone resorption and suppresses osteoblast activity. Further to its direct effects on bone cells, PTH also enhances renal calcium re-absorption and phosphate clearance, as well as renal synthesis of 1,25-dihydroxy vitamin D. Both PTH and 1,25-dihydroxyvitamin D act synergistically on bone to increase serum calcium levels and are closely involved in the regulation of the calcium/phosphate balance. The anabolic effects of PTH on osteoblasts are probably both direct and indirect via growth factors such as IGF-1 and TGF 3. The multiple signal transduction... 

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency—leading to rickets in children and osteomalacia in adults—continues to be a problem in northern latitudes, where sunlight exposure is poor. 

In a recent study, serum ascorbate concentrations were significantly reduced in a group of elderly diabetic patients (w = 40, mean age 69 years) in comparison with an age-matched group of non-diabetic controls ( = 22, mean age 71 years), and this reduction was more pronounced in those patients with microangiopathy (Sinclair et al., 1991). Diabetic patients were shown to have a high serum dehydroascorbate/ascorbate ratio indicative of increased oxidative stress. Ascorbate deficiency was partially corrected by vitamin C supplementation, 1 g daily by mouth, but the obvious disturbance in ascorbate metabolism in the diabetic patients was accentuated, since serum ascorbate concentrations fell (after the initial rise) despite continued vitamin C supplementation (Fig. 12.3). 

Coenzyme Q10 is an antioxidant essential for mitochondrial function. A dose of 1200 mg daily was associated with a slower decline in UPDRS scores than patients not receiving coenzyme Q10. Lower doses were no better than placebo, but the drug continues to be studied in doses up to 2400 mg daily. Many formulations contain vitamin E, and patients should not exceed recommended daily allowances of this vitamin, as bleeding times may be prolonged.42,43... 

High, E. G. and H. G. Day (1951). Effects of different amounts of lutein, squalene, phytol and related substances on the utilization of carotene and vitamin A for storage and growth in the rat. J. Nutr. 43 245-260. Johnson, E. J. et al. (1997). Beta-carotene isomers in human serum, breast milk and buccal mucosa cells after continuous oral doses of -trans and 9-cis beta-carotene. J. Nutr. 127(10) 1993-1999. 

D-Pantolactone and L-pantolactone are used as chiral intermediates in chemical synthesis, whereas pantoic acid is used as a vitamin B2 complex. All can be obtained from racemic mixtures by consecutive enzymatic hydrolysis and extraction. Subsequently, the desired hydrolysed enantiomer is lactonized, extracted and crystallized (Figure 4.6). The nondesired enantiomer is reracemized and recycled into the plug-flow reactor [33,34]. Herewith, a conversion of 90-95% is reached, meaning that the resolution of racemic mixtures is an alternative to a possible chiral synthesis. The applied y-lactonase from Fusarium oxysporum in the form of resting whole cells immobilized in calcium alginate beads retains more than 90% of its initial activity even after 180 days of continuous use. The biotransformation yielding D-pantolactone in a fixed-bed reactor skips several steps here that are necessary in the chemical resolution. Hence, the illustrated process carried out by Fuji Chemical Industries Co., Ltd is an elegant way for resolution of racemic mixtures. 

Yang et al. [12] determined the ionization constants of primaquine by a titrimetric method and studied its coordination ratio with vitamin C. The ionization constants of primaquine in 50% (v/v) ethanol in water determined at 25 °C in the ionic strength range of 5 x 10 to 5 x 10-2 mol/L are given. The coordination ratio of primaquine to vitamin C is determined by continuous variation and mole ratio methods based on pH and conductance measurements to be 1 1, indicating that the coordination compound formed in the solution is mainly a 1 1 compound. 

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