The vitamin D metabolome: An update on analysis and function

Abstract

Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

“…Both 25(OH)D and 1,25(OH) 2 D metabolites are catabolised and thus inactivated by CYP24A1—an enzyme primarily localised in kidneys, catalysing the hydroxylation at C-24 and C-23 of calcidiol and calcitriol, respectively [ 33 , 42 , 43 ]. The products of these reactions are then oxidised, providing water-soluble products, ultimately excreted in bile and urine [ 23 , 44 , 45 ].…”

Vitamin D Metabolism and Profiling in Veterinary Species

“…Higashi et al (2002) and Ogawa et al (2014) report a more sensitive method and were able to detect 23,25(OH) 2 D3 and 24,25(OH) 2 D3, and 25(OH)D3 and 24,25(OH) 2 D3, respectively, with lower LOQs when utilizing derivatization and pre-treating the urine with β-glucuronidase [300,301]. Glucuronidation occurs in vitamin D metabolites across the CYP24A1 pathway, and glucuronide conjugated metabolites have been demonstrated to be excreted in the bile of dogs and rats [9]. Glucuronide metabolites are highly polar and cannot be easily retained in reverse phase chromatography separation, hindering the quantitative ability of the analytical method.…”

“…Currently vitamin D status is assessed by measuring the concentration of 25-hydroxyvitamin-D (25(OH)D), owing to its relative abundance in the circulation, ease of analysis, stability, and half-life. Extensive reviews on profiling vitamin D metabolites beyond 25(OH)D in humans have recently been published [9,10]. However, there is still limited knowledge of this extensive pathway in veterinary species [11][12][13][14], and importantly, defined reference ranges for even the routinely measured 25(OH)D are lacking in most veterinary species.…”

“…An extensive network of vitamin D metabolites that contribute to the functional activity and catabolism of vitamin D in a range of diseases and tissue types are now being identified [3,9,31,32]. With improving technology, namely liquid chromatography tandem mass spectrometry (LC-MS/MS), that can facilitate the accurate identification and quantification of multiple highly similar metabolites in a single sample, it is now possible to profile the vitamin D pathway more extensively than ever before in veterinary patients [32][33][34][35][36].…”

Detection of 7-Dehydrocholesterol and Vitamin D3 Derivatives in Honey

“…Photochemical transformation of 7DHC to D3 after absorption of ultraviolet B (UVB; λ = 280-320 nm) represents a fundamental reaction for the biology of vertebrates [1][2][3]. The canonical pathway of D3 activation (D3→25(OH)D3→1,25(OH) 2 D3) that occurs in liver and kidney involves its sequential hydroxylation at C25 by CYP2R1 or CYP27A1 and at C1α by CYP27B1, producing the hormonally active 1,25(OH) 2 D3 [2,[4][5][6][7]. D3 also undergoes the same hydroxylation sequence in cells of peripheral tissues, especially skin [4,8,9].…”