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Abstract
In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC–MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC–MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.
Highlights
It was found that C3-epimers of vitamin D may have an important role to play in clinical research
Recent genetic models show that the genetic determinants and potential factors of C3-epimers differ from those of non-C3-epimers [4]
Vitamin D supplementation has recently become common, and more studies are recommended to determine the origin of epimers, either produced by exogenous sources or when metabolized endogenously; it will be beneficial to understand the nature and properties of the enzymes or tissues responsible for the epimerization process to obtain an in-depth understanding of epimers [19]
Summary
It was found that C3-epimers of vitamin D may have an important role to play in clinical research. Vitamin D supplementation has recently become common, and more studies are recommended to determine the origin of epimers, either produced by exogenous sources or when metabolized endogenously; it will be beneficial to understand the nature and properties of the enzymes or tissues responsible for the epimerization process to obtain an in-depth understanding of epimers [19]. 3-epi-25OHD3 and 3-epi-1α,25(OH)2D3 have less affinity toward DBP and even lower affinity for VDR compared to primary metabolites 25OHD3 and 1α,25(OH)2D3, which will lead to a reduction in the ability of epimers to induce calcium transport, as well as a much-reduced gene expression in the human colonic carcinoma cell line, Caco-2 [34,35]. It is known that the parathyroid hormone is suppressed by 3-epi-1α,25(OH)2D3 and that epimers are responsible for inducing phospholipid synthesis in pulmonary alveolar type II cells in comparable amounts to the non-epimeric form. Due to its weak interactions with VDR, the vitamin D epimer will remain in a free form, which might affect bodily function and give false-positive results using normal measurement methods
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