Vitamin D, referring to the two forms, D2 from the diet and D3 primarily derived from phototransformation in the skin, is a prohormone important in human health. The most hormonally active form, 1α,25-dihydroxyvitamin D (1α,25(OH)D), formed from vitamin D via 25-hydroxyvitamin D (25(OH)D), is not only important for regulating calcium metabolism, but has many pleiotropic effects including regulation of the immune system and has anti-cancer properties. The major circulating form of vitamin D is 25(OH)D and both D2 and D3 forms are routinely measured by LC/MS/MS to assess vitamin D status, due to their relatively long half-lives and much higher concentrations compared to 1α,25(OH)D. Inactivation of both 25(OH)D and 1α,25(OH)D is catalyzed by CYP24A1 and 25-hydroxyvitamin D3 3-epimerase. Initial products from these enzymes acting on 25(OH)D3 are 24R,25(OH)D3 and 3-epi-25(OH)D3, respectively, and both of these can also be measured routinely in some clinical laboratories to further document vitamin D status. With advances in LC/MS/MS and its increased availability, and with the help of studies with recombinant vitamin D-metabolizing enzymes, many other vitamin D metabolites have now been detected and in some cases quantitated, in human serum. CYP11A1 which catalyzes the first step in steroidogenesis, has been found to also act on vitamins D3 and D2 hydroxylating both at C20, but with some secondary metabolites produced by subsequent hydroxylations at other positions on the side chain. The major vitamin D3 metabolite, 20S-hydroxyvitamin D3 (20S(OH)D3), shows biological activity, often similar to 1α,25(OH)D3 but without calcemic effects. Using standards produced enzymatically by purified CYP11A1 and characterized by NMR, many of these new metabolites have been detected in human serum, with semi-quantitative measurement of 20S(OH)D3 indicating it is present at comparable concentrations to 24R,25(OH)D3 and 3-epi-25(OH)D3. Recently, vitamin D-related hydroxylumisterols derived from lumisterol3, a previtamin D3 photoproduct, have also been measured in human serum and displayed biological activity in initial in vitro studies. With the current extensive knowledge on the reactions and pathways of metabolism of vitamin D, especially those catalyzed by CYP24A1, CYP27A1, CYP27B1, CYP3A4 and CYP11A1, it is likely that many other of the resulting hydroxyvitamin D metabolites will be measured in human serum in the future, some contributing to a more detailed understanding of vitamin D status in health and disease.

Lumisterol3 (L3) is produced by photochemical transformation of 7-dehydrocholesterol (7-DHC) during exposure to high doses of ultraviolet B radiation. It has been assumed that L3 is biologically inactive and is not metabolized in the body. However, some synthetic derivatives of L3 display biological activity. The aim of this study was to test the ability of CYP11A1 to metabolize L3. Incubation of L3 with bovine or human CYP11A1 resulted in the formation of three major and a number of minor products. The catalytic efficiency of bovine CYP11A1 for metabolism of L3 dissolved in 2-hydroxypropyl-β-cyclodextrin was approximately 20% of that reported for vitamin D3 and cholesterol. The structures of the three major products were identified as 24-hydroxy-L3, 22-hydroxy-L3 and 20,22-dihydroxy-L3 by NMR. 22-hydroxy-L3 was further metabolized by bovine CYP11A1 to 20,22-dihydroxy-L3. Both 22-hydroxy-L3 and 20,22-dihydroxy-L3 gave rise to a minor metabolite identified from authentic standard and mass spectrometry as pregnalumisterol (pL) (product of C20-C22 side chain cleavage of L3) and two trihydroxy-L3 products. The capability of tissues expressing CYP11A1 to metabolize L3 was demonstrated using pig adrenal fragments where 20,22-dihydroxy-L3, 22-hydroxy-L3, 24-hydroxy-L3 and pL were detected by LC/MS. Thus, we have established that L3 is metabolized by CYP11A1 to 22- and 24-hydroxy-L3 and 20,22-dihydroxy-L3 as major products, as well as to pL and other minor products. The previously reported biological activity of pL and the presence of CYP11A1 in skin suggest that this pathway may serve to produce biologically active products from L3, emphasizing a novel role of CYP11A1 in sterol metabolism.

Lack of political commitment has been identified as a primary reason for the low priority that food and nutrition interventions receive from national governments relative to the high disease burden caused by malnutrition. Researchers have identified a number of factors that contribute to food and nutrition's 'low-priority cycle' on national policy agendas, but few tools exist to rapidly measure political commitment and identify opportunities to advance food and nutrition on the policy agenda. This article presents a theory-based rapid assessment approach to gauging countries' level of political commitment to food and nutrition security and identifying opportunities to advance food and nutrition on the policy agenda. The rapid assessment tool was piloted among food and nutrition policymakers and planners in 10 low- and middle-income countries in April to June 2013. Food and nutrition commitment and policy opportunity scores were calculated for each country and strategies to advance food and nutrition on policy agendas were designed for each country. The article finds that, in a majority of countries, political leaders had verbally and symbolically committed to addressing food and nutrition, but adequate financial resources were not allocated to implement specific programmes. In addition, whereas the low cohesion of the policy community has been viewed a major underlying cause of the low-priority status of food and nutrition, the analysis finds that policy community cohesion and having a well thought-out policy alternative were present in most countries. This tool may be useful to policymakers and planners providing information that can be used to benchmark and/or evaluate advocacy efforts to advance reforms in the food and nutrition sector; furthermore, the results can help identify specific strategies that can be employed to move the food and nutrition agenda forward. This tool complements others that have been recently developed to measure national commitment to advancing food and nutrition security.

Bioactive vitamin D3 metabolites 20S,24S-dihydroxyvitamin D3 [20S,24S(OH)2D3] and 20S,24R-dihydroxyvitamin D3 [20S,24R(OH)2D3] were chemically synthesized and confirmed to be identical to their enzymatically generated counterparts. The absolute configurations at C24 and its influence on the kinetics of 1α-hydroxylation by CYP27B1 were determined. Their corresponding 1α-hydroxyl derivatives were subsequently produced. Biological comparisons of these products showed different properties with respect to vitamin D3 receptor activation, anti-inflammatory activity, and antiproliferative activity, with 1α,20S,24R(OH)2D3 being the most potent compound.