Vitamin biological activities

The use of heteropolyacids as catalysts for fine organic synthetic processes is developing. Syntheses of antioxidants, medicinal preparations, vitamins, biologically active substances, etc., have been reported and some are already applied in practice (10, 160). 

The thiazole ring can be found in numerous molecules that possess biological activity the thiamine (vitamin B,), penicillins, antiinflamatory and bactericidals compounds, and so forth. 

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

This synthesis was the first step toward industrial vitamin production, which began in 1936. The synthetic product was shown to have the same biological activity as the natural substance. It is reversibly oxidized in the body to dehydro-L-ascorbic acid (3) (L-// fi (9-2,3-hexodiulosonic acid y-lactone), a potent antiscorbutic agent with hiU vitamin activity. In 1937, Haworth and Szent-Gyn rgyi received the Nobel Prize for their work on vitamin C. 

R)-Pantothenic acid (1) contains two subunits, (R)-pantoic acid and P-alanine. The chemical abstract name is A/-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine (11). Only (R)-pantothenic acid is biologically active. Pantothenic acid is unstable under alkaline or acidic conditions, but is stable under neutral conditions. Pantothenic acid is extremely hygroscopic, and there are stabiUty problems associated with the sodium salt of pantothenic acid. The major commercial source of this vitamin is thus the stable calcium salt (3) (calcium pantothenate). 

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). 

Many carotenoids function in humans as vitamin A precursors however, not all carotenoids have provitamin A activity (Table 3). Of the biologically active carotenoids, -carotene has the greatest activity. Despite the fact that theoretically one molecule of -carotene is a biological source of two molecules of vitamin A, this relationship is not observed and 6 p.g -carotene is equivalent to 1 p. vitamin A. Although -carotene and vitamin A have complementary activities, they caimot totally replace each other. Because the conversion of -carotene to vitamin A is highly regulated, toxic quantities of vitamin A cannot accumulate and -carotene can be considered as a safe form of vitamin A (8). 

The lUPAC-IUB Commission on Biochemical Nomenclature (13) recommends that the term vitamin B 2 be used as the genetic descriptor for aU. cottiaoids exhibiting quaUtatively the biological activity of cyanocobalamin. However, because of its commercial importance, cyaaocobalamin is used iaterchangeably with vitamin B 2 heteia. 

In 1949 the World Health Organization adopted the biological activity of 1 mg of an oil solution containing 0.025 p.g of crystalline D as the analytical standard for vitamin D. This standard was discontinued in 1972. USP uses crystalline cholecalciferol as a standard (80). Samples of reference standard may be purchased from U.S. Pharmacopeia Convention, Inc., Reference Standards Order Department, 12601, Twinbrook Parkway, Rockville, Maryland 20852. One international unit of vitamin D activity is that activity demonstrated by 0.025 ]1 of pure crystalline (7 -vitamin D. One gram of vitamin D3 is equivalent to 40 x 10 lU or USP units. The international chick unit (ICU) is identical to the USP unit. 

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. 

The biological activity of various vitamin E forms was estabUshed by the fetal resorption assay ia tats and is assumed to be appHcable to humans. The results of some human studies may iadicate that the ratio of 1.36 underestimates the biological activity of the RRR form relative to the all-rac form of a-tocopheryl acetate (10—12). 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

Summary term for a number of steroid hormones and their precursors with differentiation-inducing activity in many tissues. As regards bone, three components are relevant cholecalciferol ( vitamin D ) 25-hydroxyvi-taminD3 (calcidiol) and 1,25-dihydroxy vitamin D3 (calcitriol). The latter is the biologically active form and increases both intestinal calcium absoiption and bone resorption. Vitamin D preparations are widely used for the treatment of osteoporosis. Daily supplementation with vitamin D reduces bone loss in postmenopausal women and hip fractures in elderly subjects. 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Myo-inositol is one of the most biologically active forms of inositol. It exists in several isomeric forms, the most common being the constituent of phospholipids in biological cell membranes. It also occurs as free inositol and as inositol hexaphosphate (IP6) also known as phytate which is a major source from food. Rice bran is one of the richest sources of IP6 as well as free inositol. Inositol is considered to belong to the B-complex vitamins. It is released in the gastrointestinal tract of humans and animals by the dephosphorylation of IP6 (phytate) by the intestinal enzyme phytase. Phytase also releases intermediate products as inositol triphosphate and inositol pentaphosphate. Inositol triphosphate in cellular membrane functions as an important intra- and intercellular messenger, that merits its value as a nutritional therapy for cancer. 

---