vitamin d binding protein and monocyte response to 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d analysis by mathematical modeling维生素d结合蛋白和单核细胞反应,人体内25 -羟维生素d和1 25-dihydroxyvitamin d数学建模的分析.pdfVIP

Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling 1 2 1,3 1,3 Rene F. Chun *, Bradford E. Peercy , John S. Adams , Martin Hewison 1 UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and Orthopaedic Hospital Research Center, Los Angeles, California, United States of America, 2 Department of Mathematics and Statistics, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America, 3 Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America Abstract Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH) D) and its 2 precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH) D is difficult. To 2 address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)2D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)2D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)2D), ,0.1% 25OHD and ,1.5% 1,25(OH) D are ‘free’ in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low 2 affinity versus high affinity forms of DBP. The eSS model was then combined with an intrac