23,25-Dihydroxyvitamin D3: a natural precursor in the biosynthesis of 25-hydroxyvitamin D3-26,23-lactone.

Abstract

To elucidate the biosynthesis of 25-hydroxyvitamin D3-26,23-lactone, two One of the major metabolites of vitamin D3 has recently been detected in the plasma of vitamin D-supplemented chickens (1) and in man (2), isolated in pure form, and identified as 25-hydroxyvitamin ref. 3). This compound is not produced in nephrectomized rats, but kidney homogenate prepared from vitamin D-supplemented chickens produces it from 25-hydroxyvitamin refs. 4 and 5). Another metabolite of 25-OH-D3 was also detected during these studies; its in vivo synthesis is also abolished by nephrectomy (6). This compound was isolated in pure form and identified by spectroscopic analysis and chemical synthesis as 23, Wichmann et al. (12). All other reagents were purchased from Sigma.Animals. One-day-old single-comb White Leghorn chickens were purchased from Northern Hatcheries (Beaver Dam, WI) and fed a rachitogenic diet (13) for 1 month. For the final 3 days, they were given S ,g of 25-OH-D3 daily in 95% ethanol/propylene glycol (5:95) subcutaneously. They were also given 5 ,ug of 1,25-dihydroxyvitamin D3 in the same manner 18 hr prior to sacrifice.In Four reaction mixtures for each substrate, similarly prepared, were incubated at 370C with shaking at 100 oscillations per min for 3 hr in an atmosphere of air. The contents of the four flasks were then pooled, and the resulting 24 ml of incubation medium was extracted with 120 ml of methylene chloride (14).Purification of Extract for HPLC by Sephadex LH-20 Column. The methylene chloride extract was evaporated to dryness under reduced pressure9 and the residue was dissolved in 1 ml 23, The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

High throughput LC–MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum

“…Notably, the increasing interest in placebo-controlled supplementation trials using vitamin D3 or vitamin D2 means that it may be important to include analysis of less well characterised D2 metabolites such as 24OHD2, 1α,25(OH) 2 D2 and 3-epi-25OHD2 alongside more conventional D3 metabolites. Other vitamin D metabolites such as 23,25(OH) 2 D3 appear to play a central role in the catabolism of vitamin D [39] and may therefore provide systemic insight into the regulation of vitamin D metabolism and function. The new LC-MS/MS protocol may also be useful for cell culture experiments to elucidate vitamin D metabolism pathways for example 25OHD is frequently used as a substrate for analysis of localised, tissue-specific metabolism of 25OHD3 by cells such as macrophages [40].…”

23, 25, 26-trihydroxycholecalciferol. A 25-hydroxycholecalciferol-26,23-lactone precursor

“…This lactone has a 5-fold higher affinity for the vitamin D serum carrier protein than does 25(OH)D3 (Horst & Littledike, 1980). Consequently, 25(OH)D3-lactone could be involved in vitamin D-toxicity; or perhaps the presence of high plasma 25(OH)D3-lactone concentrations could be used as a measure of vitamin D-toxicity. 25,26(OH)2D3, a kidney microsomal metabolite of 25(OH)D3 , was initially reported as a 25(OH)D3-lactone precursor after preliminary experiments (Tanaka et al, 1981). However, rigorous investigation excluded a role for (25S)-25,26(0H)2D3, the naturally occurring isomer (Partridge et al, 1981), in 25(OH)D27lactone biosynthesis (Pramanik et al, 1981;.…”

Discovery of Candidate Serum Proteomic and Metabolomic Biomarkers in Ankylosing Spondylitis

“…25(OH)D3 26,23-peroxylactone can convert nonenzymatically into 25(OH) D3 26,23-lactone, which appears to antagonize differentiation of leukemia cell types ( 44 ). The hormonally active form of Vitamin D3 (1,25-dihydroxyvitamin D3) is itself an intermediate in the production of the lactone similar to the peroxylactone derivative identified here ( 45 ). The biological and physiological functions of the 25(OH)D3–26,23-peroxylactone are currently not fully explored, but thought to be intermediates of lactone biosynthesis ( 46 ).…”