Compartmental vitamin

In bacteria and plants, the individual enzymes of the fatty acid synthase system are separate, and the acyl radicals are found in combination with a protein called the acyl carrier protein (ACP). However, in yeast, mammals, and birds, the synthase system is a multienzyme polypeptide complex that incorporates ACP, which takes over the role of CoA. It contains the vitamin pantothenic acid in the form of 4 -phosphopan-tetheine (Figure 45-18). The use of one multienzyme functional unit has the advantages of achieving the effect of compartmentalization of the process within the cell without the erection of permeability barriers, and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene. 

The structure of ascorbic acid resembles an alpha-hydroxy acid, which is generally not appreciated. Ascorbic acid is present in most fruits, and may underlie some of the effects attributed to fruit extracts. Vitamin C has pronounced HA-stimulating effects in the fibroblast assay. But its antioxidant activity confounds the effects it may induce. The deposition of HA is stimulated when Vitamin C is added to cultured fibroblasts. The most profound changes occur in the compartmentalization of HA. The preponderance of the enhanced HA becomes cell-layer instead of being secreted into the medium.240,261 The chemical reactions catalyzed by ascorbic acid that bind HA to cell or matrix components are not known. 

Our defenses against oxygen toxicity fall into the categories of antioxidant defense enzymes, dietary and endogenous antioxidants (free radical scavengers), cellular compartmentation, metal sequestration, and repair of damaged cellular components. The antioxidant defense enzymes react with ROS and cellular products of free radical chain reactions to convert them to nontoxic products. Dietary antioxidants, such as vitamin E and flavonoids, and endogenous antioxidants, such as urate, can... 

Whole-Body Models for Vitamin A Metabolism Empirical Compartmental Analysis of Vitamin A Metabolism Liver Vitamin A Metabolism... 

FIG. 6. Compartmental model proposed by Green et al. (1993) for liver and whole-body vitamin A metabolism. Compartment 11 is plasma retinol. PC, parenchymal cells NPC, nonparenchymal cells (assumed here to be perisinusoidal stellate cells) ROH, retinol RE, retinyl esters CM, chylomicrons. 

Green, M. H., Green, J. B., and Lewis, K. C. (1992). Model-based compartmental analysis of retinol kinetics in organs of rats at different levels of vitamin A status. In Retinoids Progress in Research and Qinical Applications (M. A. Livrea and L. Packer, eds.), pp. 185-204. Dekker, New York. 

The residence time for retinol in the test subject was predicted by the compartmental model to be 474 days. The residence time of 474 days is in excellent agreement with the 460 day MST that can be calculated from the data of Song et al. (1995) using the enrichment ratio method (Cobelli and Saccomani, 1992). Also, an MST of 105 to 337 days can be calculated from the half-life values (75 to 241 days) of body vitamin A reported by Sauber-lich et al. (1974) who depleted human subjects with vitamin A-deficient diets. At the same time the empirical description predicted the MST for retinol to be 26 days. While the reason for such a large discrepancy in MST (474 versus 26 days) between the compartmental model and the empirical description prediction is unclear, it is not likely to be accounted for by slight errors in estimating the final slope of the plasma retinol-d4 decay curve. Because the compartmental model embodies several features of retinol metabolism de novo production and release of retinol can occur in unobservable compartments, etc.) in addition to plasma retinol concentrations, its predicted MST is more likely to better reflect the dynamics of retinol metabolism. 

The compartmental model was also able to predict the efficiency of conversion of /3-carotene to vitamin A in our subject. The model predicted that 1 (ig dietary /3-carotene yielded 0.054 /ug retinol (the same as 0.101 /unol retinol/pimol /3-carotene). The 0.054-/i4g value is considerably lower than the 0.167 fig retinol//ug /3-carotene which is widely accepted. However, the 0.167-/iig value was established in growing rats with low reserves of retinol who were adapted to maximizing the retinol yield (Brubacher and Weiser, 1985). If our subject had been in marginal or deficient vitamin A status, the predicted yield would probably have exceeded 0.054 fig retinol//ig /3-carotene. Further studies are needed to determine the influence of vitamin A status on conversion of /3-carotene to vitamin A and the ability of dietary carotene to maintain tissue retinoid. 

Questions regarding the extent of postabsorptive bioconversion of /3C to vitamin A persist. Animal data indicate the liver possesses this capability, but the relative importance of intestinal mucosa versus liver is unknown. Novotny and co-workers (1995) reported a compartmental model which predicted that both liver and intestinal mucosa were important sites for biotransformation of /SC in the human, with 43% of total conversion occurring in the liver and 56% in the intestinal mucosa. However, the model assumed a stoichiometry of 1 mol retinol per mole /SC, and the effect on the model assuming a 2 1 ratio was not discussed. 

Lipophilic metabolites tend to accumulate within the production host. If in addition the metabolite is colored or fluorescing, a carotenoid for instance, flow cytometry-based cell sorting protocols are suited to isolate individuals with improved production traits out of a mutagenized population, even if they are present at very low frequency. Value compounds typically produced with B. subtilis production hosts, such as water-soluble vitamins, purine nucleosides, ribose, or proteins, are secreted and accumulate in the culture medium. Screening of improved production strains for such metabolites requires clonal cultivation of the members of the mutagenized population in compartmentalized reactors and individual analyses of the culture supernatants in each of the reactors. 

Several factors can be manipulated to control and reduce flavor deterioration in meat due to lipid oxidation. Factors related to raw material include vitamin E content and age, while factors related to processing include addition of antioxidants, heat treatment and packaging. Oxidation in meat and other muscle foods is promoted by any processing that disrupts the natural cellular compartmental separation that controls oxidation. Heating and grinding raw meat thus accelerate lipid oxidation. It is therefore important to maintain the integrity of heated meat products to retard flavor deterioration from lipid oxidation. 

These results are apparently irreconcilable with other studies that show that when xanthine oxidase activity does increase above normal (e.g., in tumor-bearing rats, vitamin E deficiency, and some virus infections) there is always a proportionate increase in allantoin excretion. This increase may be as much as tenfold and is too great to be accounted for by increased nucleic acid turnover under these conditions. Xanthine oxidase activity also increases upon refeeding after starvation, and this has been shown to be due to new RNA and protein synthesis SI). These results raise questions concerning intracellular compartmentation, enzyme latentiation, etc., that have yet to be answered. 

Lewis KC, Green MH, Green JB, Zech LA (1990) Retinol metabolism in rats with low vitamin A status a compartmental vaodeX. J Lipid Res 31 1535-1548... 

Von Reinersdorff D, Green MH, and Green JB (1998) Development of a compartmental model describing the dynamics of vitamin A metabolism in men. Advances in Experimental Medicine and Biology 445 207-223. 

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