1α,23(S),25-trihydroxy-24-oxovitamin D₃

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 1α,23(S),25-trihydroxy-24-oxovitamin D₃
• 英文别名: 1α,23(S),25-trihydroxy-24-oxovitamin-D₃；1α,23(S),25-trihydroxy-24-oxo-vitamin D3；1α,23(S),25-trihydroxy-24-oxovitamin D3；1α,23(S),25(OH)3-24-oxo-D₃；24-oxo-1α,23,25-trihydroxyvitamin D3；(23S)-1alpha,23,25-trihydroxy-24-oxovitamin D3/(23S)-1alpha,23,25-trihydroxy-24-oxocholecalciferol；(4S,6R)-6-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-2,4-dihydroxy-2-methylheptan-3-one
• 化学式: C₂₇H₄₂O₅
• 分子量: 446.627
• InChiKey: ARRIBDAUGOLZSJ-LOLJMGAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  98
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  骨化三醇 在 bovine adrenodoxin reductase 、 bovine adrenodoxin 、 recombinant rat cytochrome P450 24A1(Δ2-32) 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 0.08h， 生成 (3R,5S)-5-[(2R)-2-[(1R,3aR,4E,7aR)-4-[(2Z)-2-[(3S,5S)-3,5-二羟基-2-亚甲基-环己基亚基]乙亚基]-7a-甲基-2,3,3a,5,6,7-六氢-1H-茚-1-基]丙基]-3-羟基-3-甲基-四氢呋喃-2-酮 、 1,23-二羟基-24,25,26,27-四去甲维他命 D3 、 1,25-二羟基-24-氧代-维他命D3 、 (24R)-1(alpha),24,25-三羟基维他命 D3* 、 1α,23(S),25-trihydroxy-24-oxovitamin D₃
  参考文献：
  名称：

  A new insight into the role of rat cytochrome P450 24A1 in metabolism of selective analogs of 1α,25-dihydroxyvitamin D3

  摘要：

  We examined the metabolism of two synthetic analogs of 1 alpha,25-dihydroxyvitamin D-3 (1), namely 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D-3 (2) and 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-dimethyl-vitamin D-3 (4) using rat cytochrome P450 24A1 (CYP24A1) in a reconstituted system. We noted that 2 is metabolized into a single metabolite identified as C26-hydroxy-2 while 4 is metabolized into two metabolites, identified as C26-hydroxy-4 and C26a-hydroxy-4. The structural modification of adding methyl groups to the side chain of 1 as in 4 is also featured in another analog, 1 alpha,25-dihydroxy-22,24-diene-24,26,27-tri-homo-vitamin D-3 (6). In a previous study, 6 was shown to be metabolized exactly like 4, however, the enzyme responsible for its metabolism was found to be not CYP24A1. To gain a better insight into the structural determinants for substrate recognition of different analogs, we performed an in silico docking analysis using the crystal structure of rat CYP24A1 that had been solved for the substrate-free open form. Whereas analogs 2 and 4 docked similar to 1,6 showed altered interactions for both the A-ring and side chain, despite prototypical recognition of the CD-ring. These findings hint that CYP24A1 metabolizes selectively different analogs of 1, based on their ability to generate discrete recognition cues required to close the enzyme and trigger the catalytic mechanism. 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2011.02.004

文献信息

• A new insight into the role of rat cytochrome P450 24A1 in metabolism of selective analogs of 1α,25-dihydroxyvitamin D3
  作者：Steve Y. Rhieu、Andrew J. Annalora、Rose M. Gathungu、Paul Vouros、Milan R. Uskokovic、Inge Schuster、G. Tayhas R. Palmore、G. Satyanarayana Reddy

  DOI：10.1016/j.abb.2011.02.004

  日期：2011.5

  We examined the metabolism of two synthetic analogs of 1 alpha,25-dihydroxyvitamin D-3 (1), namely 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D-3 (2) and 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-dimethyl-vitamin D-3 (4) using rat cytochrome P450 24A1 (CYP24A1) in a reconstituted system. We noted that 2 is metabolized into a single metabolite identified as C26-hydroxy-2 while 4 is metabolized into two metabolites, identified as C26-hydroxy-4 and C26a-hydroxy-4. The structural modification of adding methyl groups to the side chain of 1 as in 4 is also featured in another analog, 1 alpha,25-dihydroxy-22,24-diene-24,26,27-tri-homo-vitamin D-3 (6). In a previous study, 6 was shown to be metabolized exactly like 4, however, the enzyme responsible for its metabolism was found to be not CYP24A1. To gain a better insight into the structural determinants for substrate recognition of different analogs, we performed an in silico docking analysis using the crystal structure of rat CYP24A1 that had been solved for the substrate-free open form. Whereas analogs 2 and 4 docked similar to 1,6 showed altered interactions for both the A-ring and side chain, despite prototypical recognition of the CD-ring. These findings hint that CYP24A1 metabolizes selectively different analogs of 1, based on their ability to generate discrete recognition cues required to close the enzyme and trigger the catalytic mechanism. 2011 Elsevier Inc. All rights reserved.