This book is based on experimental work performed at Aarhus University. The work was conducted to gain insight into the cellular endocytosis and export of vitamin B12. Vitamin B12 (cobalamin) is an organic molecule which functions as an essential coenzyme for two metabolic reactions in mammalians. Cellular vitamin B12 uptake is a complex process involving different binding proteins and receptors. The studies revealed that the endocytosis of transcobalamin bound to fluorescent vitamin B12 conjugate is correlated with cell growth in fast dividing cancer cells and the uptake of free vitamin B12 was negliable at low as well as high cell division activity. Furthermore this study provides evidenced that vitamin B12 is exported to the cellular environment as a free molecule and the binding to a carrier protein occur subsequently to export, and a novel transporter for the cellular export of vitamin B12 was identified. In conclusion, this PhD study provides new information on the cellular vitamin B12 import and in particular export by revealed a novel transport mechanism of non-protein bound vitamin B12 and the identification of a transporter protein for this process.
Vitamin B12 (cobalamin) is an essential micronutrient and an important cofactor in the one-carbon metabolism. Vitamin B12 has been meticulously studied for decades, and much is known concerning the uptake and actions of this vitamin. However, several aspects still need to be clarified in order for us to understand its role in health and disease. In pursue of pieces for the puzzle, I have addressed three unresolved facets of the cobalamin metabolism in this work: The presence of vitamin B12-binding proteins in fish (Part A); Vitamin B12 during pregnancy and infancy (Part B); and the effects of metformin treatment on vitamin B12 metabolism (Part C).
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Intake of vitamin B12 for three consecutive weeks had no effect on the weight or body shape of the mice. Also, no toxic effects were observed during the experiment. Intake of vitamin B12 (0.8 mg / kg body weight) before irradiation improved the mortality rate, when compared to the untreated irradiated group and the best improvement was observed at day 14 after irradiation. Intake of vitamin B12 prior to irradiation improved the rate of mitotic index. The best recoveries in mitotic index rate were at 6 and 72 hr after irradiation. Treatment with vitamin B12 prior to irradiation increased the total number of polychromatic erythrocytes (PCEs) by 17 % and decreased the total incidence of normochromatic erythrocytes (NCEs) by 4 folds. Intake of vitamin B12 prior to irradiation revealed a highly significant decrease in the morphological deformation of sperm head and tail by 1.4 folds.
Recurrent Aphthous Stomatitis RAS)is a very common disease which carries no mortality but a high morbidity. Incidence of RAS varies from 5% to 50% depending on the ethnic and socioeconomic groups. The most commonly affected population is 10-40 years, who belong to either mid or high socioeconomic class with equal distribution in males and females. RAS is a multifactorial disease and there are several precipitating factors of which stress is the most important. Other associated factors are lack of sleep, minor trauma to oral mucosa in susceptible individuals, menstruation, constipation and food allergies. Although the effect of vitamin B12 and folic acid deficiency was not significant; the combined effect of vitamin B12 deficiency with stress and that of iron deficiency with trauma precipitated the RAS. It is always important to rule out malabsorption syndromes and other systemic diseases in case of haematinic deficiencies.