Background: Calcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency.
Methods: We evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2-5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20).
Results: The geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or ≥20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating.
Conclusion And General Significance: In conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations.
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http://dx.doi.org/10.1016/j.bbacli.2015.03.004 | DOI Listing |
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFFood Chem
January 2025
Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences/Institute of Agro-bioengineering, Guizhou University, Guiyang 550025, China. Electronic address:
Nanozyme-based sensors for detecting ascorbic acid (AA) generally depend on the reducibility of the analyte. However, these sensors are susceptible to interference from reducing substances in food. Herein, a novel fluorescent sensor for AA detection was developed based on inhibiting the phosphatase-like activity of a Zr-based metal-organic framework (Zr-CAU-28).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
School of Applied Sciences, College of Health, Science and Society, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK.
The active metabolite of vitamin D3, calcitriol (1,25D), is widely recognised for its direct anti-proliferative and pro-differentiation effects. However, 1,25D is calcaemic, which restricts its clinical use for cancer treatment. Non-calcaemic agonists of the vitamin D receptor (VDR) could be better candidates for cancer treatment.
View Article and Find Full Text PDFBMJ Case Rep
January 2025
Pediatrics, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India.
Rickets in children usually present with skeletal manifestations. However, they can also rarely present with extraskeletal manifestations, one of them being respiratory insufficiency. We present an unusual case of a girl in early childhood with respiratory insufficiency, which turned out to be due to the underlying vitamin D-dependent rickets (VDDR).
View Article and Find Full Text PDFPhysiol Mol Biol Plants
December 2024
Department of Fruit Science, College of Horticulture and Forestry, CAU (I), Pasighat, Arunachal Pradesh 791102 India.
An experiment was performed to understand the effects of aluminium toxicity (AlCl·6HO) on Kachai lemon growth and development. The toxic effects of aluminium were assessed for 45 days in sand media. With untreated pots serving as the control, seedlings of 1 month old were exposed to three concentrations of AlCl·6HO: 300 μM, 600 μM and 900 μM.
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