Diploma Thesis from the year 2002 in the subject Chemistry - Bio-chemistry, grade: very good, University of Vienna (Institute for pharmaceutical Chemistry), language: English, abstract: 1. INTRODUCTION1.1. General aspects of Vitamin D1.1.1. Synthesis and MetabolismVitamin D in the human body exists in two forms, derived from twosources. In the form of Vitamin D3, it is generated from 7-dehydrocholesterol inthe skin by exposure to ultraviolet light (270-300 nm range), and in the form ofVitamin D2 or Vitamin D3 (Fig. 1), it can be derived from diet. [...] Both forms of Vitamin D are precursor of functionally active hormonesand undergo the same two-step activation process leading to 1,25-(OH)2-D2 or 1,25-(OH)2-D3, respectively. These metabolic activations of Vitamin D3 arecarried out a by specific P-450-containing enzymes, the vitamin D3-25-hydroxylase (CYP27A) and the 25-hydroxyvitamin D-1-hydroxylase(CYP27B1). Both hydroxylases are located in the inner mitochondrialmembrane of cells (Fig. 2).There is little evidence that the two hormones differin their mode of action (Jones et al. (1998)).In contrast to earlier assumptions, which strictly localized 25-hydroxylation in the liver and sequential 1hydroxylation in the kidney (Blunt etal. (1968)), many different cell types were shown to be capable of the two-stepactivation process too. Regulation of both enzymes appears to be tissuespecific:CYP27A is only loosely regulated (Bhattacharyya et DeLuca (1973)) orconstitutively expressed (Schüssler et al. (2001)). 1-Hydroxylase in the kidneyis tightly regulated by the levels of plasma 1,25-(OH)2D3 and calcium (via theparathyroid hormone (PTH)) (reviewed by Jones et al. (1998)), howeverconstitutively expressed in skin (Schüssler et al. (2001)). A third vitamin Drelatedmitochondrial cytochrome P-450-containing enzyme is the 25-hydroxyvitamin D-24-hydroxylase (CYP24). This enzyme is strongly inducibleby 1,25-(OH)2-D3 in practically all cell types of the body, prefers 1,25-(OH)2-D3 as a substrate over 25-OH-D3, and catalyzes several steps of 1,25-(OH)2-D3 metabolism, collectively known as the C-24 oxidation pathway (Fig.3.,Reddy and Tserng, 1989; Makin et al., 1989). [...]