Browsing by Subject "Intracellular distribution"

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Tocotrienols, tocopherols and tocomonoenols : characterization in Costa Rican palm oils, and intracellular and tissue distribution as a function of the hepatic alpha-tocopherol transfer protein
(2018) Irías-Mata, Andrea Paola; Frank, Jan
Vitamin E is a generic term for a group of micronutrients exhibiting the biological activity of alpha-tocopherol. Initially, four tocopherols (T) and four tocotrienols (T3) were recognized as the naturally occurring vitamin E compounds. The main difference among T and T3 is the 3-fold unsaturated 16-carbon side chain of the T3 compared to the saturated 16-carbon side chain of the T. Recently, a group of four vitamin E compounds with a single double bond at carbon 11 were discovered, namely tocomonoenols (T1). Edible oils are the major source of T, T3, and of T1. As a fat-soluble vitamin, the vitamin E is absorbed after oral intake and transported in the circulation to the liver, where vitamin E undergoes sorting by the action of the alpha-hepatic-tocopherol transfer protein (TTP) and the cytochrome P450 (CYP) enzymes. alpha-T is preferentially secreted into the bloodstream, while the non-alpha-T congeners are metabolized by CYP to the carboxyethylhydroxychromanols (CEHC), which are excreted via urine and feces. The TTP has been recognized as necessary for the maintenance of normal alpha-T concentrations in plasma and extrahepatic tissues. Interestingly, TTP might also protect the non-alpha-T congeners from side-chain degradation, and therefore prevent their metabolic degradation. The present thesis aimed at increasing our knowledge of the non-αT congeners of vitamin E with respect to their occurrence in food, their intracellular localization upon uptake into liver cells, and their tissue distribution in mammals. A potential role of the TTP in the intracellular and intra-organismic trafficking of the non-alpha-T congeners was a second focus of the current investigations. To this purpose, the vitamin E profiles and contents in oils of three Elaeis Guineensis, two Elaeis Oleifera, and one hybrid OxG palm fruit genotypes from Costa Rica were determined after mechanical extraction with a screw press and chemical extraction with hexane. Vitamin E profiles in the palm oils were similar, irrespective of the genotype and extraction procedure, and alpha- and gamma-T3 were the most abundant congeners. alpha-T1 was found in oils from five of the six varieties. Hexane extraction yielded up to 2.5-fold higher total vitamin E compared to screw press extraction. The two most abundant tocotrienols in the oils were selected for further studies with respect to their cellular uptake and intracellular distribution in cultured liver cells with and without stable expression of TTP and compared to their respective tocopherol counterparts. After uptake, all four congeners were primarily associated with the lysosomes, endoplasmic reticulum and plasma membrane. Overall, the results conclude that neither the structural differences between the four congeners, nor the TTP-expression are important factors behind the intracellular trafficking (uptake and distribution) of the congeners in cultured liver cells. Finally, an animal study was performed to examine the tissue distribution of alpha-T1 in mice in comparison to alpha-T. Besides was investigated the influence of TTP. Wild-type and TTP knockout mice were fed a standard diet with either alpha-T or alpha-T1 for 2 weeks. Concentrations were measured in blood and several tissues. alpha-T1 was only found in blood, not in tissues. Loss of TTP function in knockout mice resulted in almost complete depletion of alpha-T in all tissues. Interestingly, alpha-T1 was still present in blood. In conclusion, alpha-T1 reached the blood in mice with and without TTP function, suggesting that TTP may not, or only to a limited extent, be required for the secretion of alpha-T1 into the systemic circulation. Since more is known about alpha-T than the non-alpha-T congeners, new opportunities for further research on the biological activities and consequent health benefits of the non-alpha-T congeners have arisen based on the contributions of the present thesis.