Compartmental modeling vitamin

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. 

Lewis, K. C Green, M. H., Green, J. B and Zlech, L. A. (1990). Retinol metabolism in rats with low vitamin A status A compartmental model. J. Lipid Res. 31,1S3S-1348. 

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. 

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. 

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

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