Triacyglycerol (TG) is a major caloric source for the body and its malabsorption signals the development of a disease state. Although a large body of information exists on lipid absorption, little information is available on factor influencing lipid transport from the intestine. This proposal focuses on this tissue. Preliminary studies have found that phosphatidylcholine (PC) included in triacylglycerol (TG) infusions is of major importance in the delivery of TG to lymph. Two sets of experiments have been designed to study why PC is important to TG transport. In the first, de novo and lyso PC derived PC synthetic rates, turnover rates and PC precursor pool sizes will be investigated under varying conditions of de novo PC synthetic demands. A second series of experiments will investigate the reason why de novo PC synthesis cannot keep pace with demand. These studies will include an enzymological investigation of the 3 enzymes of de novo PC synthesis: choline kinase, CTP: phosphocholine cytidylyltransferase and phosphocholine transferase. Enzyme activity will be carefully correlated with demand for de novo PC synthesis and stimulators of activity identified. These studies will identify in what physiologic setting de novo PC synthesis becomes limiting and pinpoint the likely limiting step. Two other potential limiting factors in TG delivery will be studied. TG synthetic rates have been shown to be important in that lymphatic recoveries of infused (14C oleoyl) TG have been poor at high TG infusion rates indicating transport as FFA, not TG. These rates and the route of TG synthesis in the mucosa either from monoacylglycerol or from de novo sources have been shown to influence the entry of TG into a rapidly transported or slowly transported TG pool. The slowly transported pool may efflux TG into the lumen of the bowel and has been shown to contribute to lipid malabsorption. Therefore, factors controlling this partition will be studied. Another limiting factor in TG export is apolipoprotein B synthesis. The synthetic rates of this apolipoprotein will be studied in several physiological conditions. These studies will improve our understanding of factors controlling TG export. Advantage can be taken of this knowledge to improve lipid delivery in states where bile and/or PC delivery (defined enteric feeding) to the intestine is reduced. Improved TG transport may also lead to less steaotorrhea secondary to less TG efflux if the factors controlling TG export can be modulated.
| Mansbach 2nd, C M; Arnold, A; Garrett, M (1987) Effect of chloroquine on intestinal lipid metabolism. Am J Physiol 253:G673-8 |
| Mansbach 2nd, C M; Rosen, G M; Rahn, C A et al. (1986) Detection of free radicals as a consequence of rat intestinal cellular drug metabolism. Biochim Biophys Acta 888:1-9 |
| France Jr, H G; Jirtle, R L; Mansbach 2nd, C M (1986) Intracolonic WR 2721 protection of the rat colon from acute radiation injury. Gastroenterology 91:644-50 |
| Mansbach 2nd, C M; Arnold, A (1986) CTP:phosphocholine cytidylyltransferase in intestinal mucosa. Biochim Biophys Acta 875:516-24 |
| Mansbach 2nd, C M; Arnold, A (1986) Steady-state kinetic analysis of triacylglycerol delivery into mesenteric lymph. Am J Physiol 251:G263-9 |
| Mansbach 2nd, C M; Arnold, A; Cox, M A (1985) Factors influencing triacylglycerol delivery into mesenteric lymph. Am J Physiol 249:G642-8 |
| Dunstan, R A; Mansbach 2nd, C M (1985) Biochemical characterisation of A blood group activity on human platelets. Vox Sang 49:149-53 |
