Lipid soluble vitamins

See also Antioxidants, Reactive Oxygen, Oxygen Metabolism and Human Disease, Vitamins, Lipid-Soluble Vitamins... 

Selected applications of coupled SEE-SEC consider the analysis of tocopherols in plants and oil by-products (65) or the analysis of lipid-soluble vitamins (66) by using a dynamic on-line SEE-SEC coupling, integrated in the SE chromatograph, based on the use of micropacked columns. 

In vitro and ex vivo studies have shown that FATPs transport LCFAs and very long-chain fatty acids (VLCFAs) but no medium-chain fatty acids, fatty acid esters, or lipid-soluble vitamins [4]. LCFA transport is inhibited by prior protease treatment. Synthetic substrates for FATPs include 14C-labeled fatty acids and the fluorescently labeled fatty acid analogue C1 -BODEP Y-Cl 2. Using the latter substrate, differences in fatty acid uptake kinetics between FATP expressing 3T3 LI adipocytes and 3T3 LI fibroblasts, which are devoid of FATPs, can be readily appreciated (Fig. 2). 

Thiamin has a very low toxicity (oral LD5o of thiaminchloride hydrochloride in mice 3-15 g/kg body weight). The vitamin is used therapeutically to cure polyneuropathy, beri-beii (clinically manifest thiamin deficiency), and Wernicke-Korsakoff Syndrome ( Wernicke encephalopathy and Korsakoff psychosis). In mild polyneuropathy, 10-20 mg/d water-soluble or 5-10 mg/d lipid-soluble thiamin are given orally. In more severe cases, 20-50 mg/d water-soluble or 10-20 mg/d lipid-soluble thiamin are administered orally. Patients suffering from beri-beri or from early stages of Wernicke-Korsakoff Syndrome receive 50-100 mg of thiamin two times a day for several days subcutaneously or intravenously until symptoms are alleviated. Afterwards, the vitamin is administered orally for several weeks. 

Vitamin E is the Major Lipid-Soluble Antioxidant in Cell Membranes Plasma Lipoproteins... 

Natural antioxidants may be classified according to their nutritive value or according to their solubility. The hydrophobic vitamin E and the hydrophilic vitamin C are thus important both as nutrients and as antioxidants. The nonnutritive antioxidants may similarly be divided into lipid-soluble and water-soluble antioxidants, as shown in Fig. 16.3, which will also form the basis for a discussion of exploitation of combinations of anhoxidants in order to improve protective effects. 

Nonaqueous Systems In nonaqueous (nonpolar) solvent systems, nitrosatlon also proceeds. In these solvents, alpha-tocopherol acts as a lipid soluble blocking agent in much the same fashion as ascorbic acid functions in the aqueous phase. Alpha-tocopherol reacts with a nitrosating agent and reduces it to nitric oxide. At the same time, alpha-tocopherol is oxidized to tocoquinone, which is the first oxidation product of vitamin E and also a normal metabolite in vivo. 

Burton, G., Joyce, A. and Ingold, K.U. (1983). Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes Arch. Biochem. Biophys. 221, 281-290. 

The major lipid-soluble antioxidant primarily associated with lipid membranes is a-tocopherol (vitamin E). Circulating a-tocopherol is carried by chylomicrons, LDL and HDL and also has extracellular antioxidant capacities. As a chain-breaking antioxidant, it short circuits the propagation phase of lipid peroxidation because the peroxyl radical will react with a-tocopherol more rapidly than a polyunsaturated ffitty acid (Burton and Traber, 1990). The resulting a-tocopheryl radical reacts with a second peroxyl radical to form an inactive, nonradical complex. In vitro, ascorbate regenerates the tocopheryl radical into its native non-radical form (Burton and Traber, 1990). 

The importance of vitamin E for maintenance of lipid integrity in vivo is emphasized by the fact that it is the only major lipid-soluble chain-breaking antioxidant found within plasma, red cells and tissue cells. Esterbauer etal. (1991) have shown that the oxidation resistance of LDL increases proportionately with a-tocopherol concentration. In patients with RA, synovial fluid concentrations of a-tocopherol are significantly lower relative to paired serum samples (Fairburn et al., 1992). The low level of vitamin E within the inflamed joint implies it is being consumed via its role in terminating lipid peroxidation and this will be discussed further in Section 3.3. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

Vitamin E (tocopherol), which is a major lipid-soluble antioxidant, inhibits the differentiation of smooth muscle presumably by modulating the activity of protein kinase C. PKC inhibition by tocopherol has also been implied in human platelets. 

Vitamins have historically been classified as either water soluble or lipid soluble. Water-soluble vitamins are precursors for coenzymes and are reviewed in the context of the reactions for which they are important A summary of these vitamins is shown in Table I-lO-l. 

There are four important lipid-soluble vitamins, D, A, K, and E. Two of these vitamins, A and D, work through enhancer mechanisms similar to those for lipid-soluble hormones. In addition, all four lipid-soluble vitamins have more specialized mechanisms through which they act. Table 1-10-2 lists their major functions. 

Vitamin (a-tocopherol) is an antioxidant. As a lipid-soluble compound, it is especially important for protecting other lipids from oxidative damage. 

Vitamin D is a lipid-soluble vitamin, as is vitamin A. Lipid-soluble vitamins are stored in the body, in contrast to water-soluble vitamins such as vitamin C. Excess consumption of lipid-soluble vitamins can result in excess storage and resultant toxicity. The UL for vitamin D is 50 micrograms/day. Excess consumption may raise the blood level of calcium to the extent that calcification of organs (particularly the kidneys), occurs, and formation of kidney stones may follow. 

The food components resorbed by the epithelial cells of the intestinal wall in the region of the jejunum and ileum are transported directly to the liver via the portal vein. Fats, cholesterol, and lipid-soluble vitamins are exceptions. These are first released by the enterocytes in the form of chylomicrons (see p. 278) into the lymph system, and only reach the blood via the thoracic duct. 

Vitamins are classified as either lipid-soluble or water-soluble. The lipid-soluble vitamins include vitamins A, D, E, and K, all of which belong to the isoprenoids (see p. 52). 

---