The term vitamin A describes a group of chemical compounds, which show similar structural characteristics (ß-ionone ring and isopropyl side chain) and directly or indirectly reveal vitamin A functions. The transport form and the central metabolite of the vitamin A family is retinol, which can be metabolized to the active metabolites retinal aldehyde (retinal) and retinoic acid by oxidation. Retinal is a chromophore and an integral component of the visual purple (rhodopsin) in the retina and therefore of crucial significance for the visual process. Retinoic acid in contrast functions as transcription factor that regulates gene expression and is thus significantly involved in numerous central processes like the immune function, cell differentiation, reproduction and embryonal development1,2.
Vitamin A has to be supplied with the diet and will, after the uptake via the gastrointestinal tract, be stored in the liver in form of retinyl esters (predominantly retinyl palmitate). These storage sites can be mobilized by hydrolyzation and the released retinol will be secreted into the circulation. For this purpose prior to the hepatic secretion retinol binds the retinol binding protein 4 (RBP4), which facilitates the transport of the lipophilic ligand in the watery environment of the blood and protects it at the same time from oxidative damage. To prevent the loss of this low-molecular weight complex of retinol and RBP4 (holo-RBP4, ca. 21. kDa) due to renal filtration, it will furthermore bind to the protein transthyretin (TTR). The resulting trimolar structure with a molecular weight of approximately 75 kDa will then facilitate the transport of vitamin A (retinol) to the target tissues, where it will be taken up via the membrane receptor STRA6 (Stimulated by Retinoic Acid 6). The remaining complex of apo-RBP4 and TTR falls apart and will be catabolized renally1-4.
Due to the complexity of the vitamin A metabolism physiological or pathophysiological events on a systemic level or in isolated organ systems can cause an imbalance of the vitamin A metabolism and consequently represent an are of focus of the department.
Carotenoids are yellow and orange, organic pigments, which can exclusively be synthesized by plants and microalgae, in which they mainly assist photosynthesis. More than 800 carotenoids are known that are classified as carotenes and xanthophylls. For humans especially the carotenes α-carotene, β-carotene, β-cryptoxanthene and lycopene as well as the xanthophylls lutein and zeaxanthin are of significant importance and therefore in the focus of the department`s research. α- and β-carotene as well as β-cryptoxanthene serve as provitamin A carotenoids in the supply with vitamin A for humans. Whereas lutein and zeaxanthin are important for the protection of the retina against damages by UV light and radicals and therefore for the prevention of age-related macular degeneration (AMD). Furthermore all carotenoids are natural antioxidants and therefore valuable food compounds1-3.
The significance of carotenoids for the human organism is researched in the department of Physiology and Pathophysiology of Nutrition under several aspects:
No other vitamin is currently being researched as intensely as vitamin D. This research interest can mainly be attributed to new effects of vitamin D on the organism, which have been discovered in the recent years in addition to the known effects on the bone health.
Especially during the winter months in the northern hemisphere a great part of the population shows a reduced vitamin D status1,2. The recently investigated and discussed diseases as a result of reduced vitamin D status and vitamin D deficiency, respectively, are attributed to the non-calcaemic effects of vitamin D. This includes for example diabetes mellitus, cancer, cardiovascular disease and diseases of the immune system3. The underlying, responsible mechanisms in this context are so far not completely understood4 and therefore object of many research activities.
One main area of research at the department of Physiology and Pathophysiology of Nutrition is the investigation regarding the association of vitamin D and kidney diseases. The quantification of different vitamin D metabolites is one approach of the department to solve this question.
Further research activities pursue the analysis of the connection between the vitamin D status, kidney diseases and cardiovascular diseases by using in vitro models systems to analyze the integrity of vessels depending on the vitamin D supply and simulating conditions of kidney disease.
The term vitamin E includes all natural and synthetic tocopherol and tocotrienol derivatives, which show qualitatively the biological activity of α-tocopherol. In animal cells α-tocopherol is a compound of biological membranes, where it serves as fat soluble antioxidant. The important biological antioxidant function of vitamin E is to protect membrane lipids, lipoproteins and depot fats from lipid peroxidation.
Vitamin E is an essential nutrient and therefore has to be supplied with the food. The absorption of vitamin E occurs in the small intestine together with other food lipids. The transport in the blood occurs, in contrast to the vitamins A and D, unspecifically by binding to the lipoprotein fractions (VLDL/LDL, HDL). The uptake of vitamin E into the cells is therefore strongly related to the lipoprotein metabolism.
Due to the central position of vitamin E as lipophilic antioxidant, analyses regarding the influence of different physiological and pathophysiological conditions on the vitamin E metabolism are a focus area of our department. The basis is formed by the quantification of tocopherol and tocotrienol derivatives in blood and tissue of humans and pets using HPLC. In this context we were able to demonstrate in a prospective study that patients that suffer from type 2 diabetes mellitus requiring dialysis and that reveal a reduced α-tocopherol concentration in blood have an increased risk for strokes1. Further studies focused on the transfer of α-tocopherol from blood into the ovarian follicle in women2 as well as the measurement of α-tocopherol losses via the ascites liquid of women with progressing ovarian carcinoma3. If a supplementation of vitamin E has an influence on the progress of the disease continues to be a research focus.
The adequate supply of vitamin E with the food is also of significant importance for pet animals to maintain their health. In this context our department demonstrated that dogs are able to absorb different tocopherol and tocotrienol derivatives in the gut and that the associated increase in the blood is accompanied by an increase of antioxidant capacity4. If a dietetic supplementation with tocotrienols has a positive effect on the progression of diseases with increased oxidative stress, will be analyzed in further studies.