4alpha-Carboxyzymosterol(1-)

• 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: 4alpha-Carboxyzymosterol(1-)
• 英文别名: (3S,4S,5S,10S,13R,14R,17R)-3-hydroxy-10,13-dimethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,4,5,6,7,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-4-carboxylate
• 化学式: C28H43O3-
• 分子量: 427.6
• InChiKey: JHIWIFRQJXLNEU-GSQAGGHASA-M

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4alpha-Carboxyzymosterol(1-) 、 nicotinamide adenine dinucleotide 生成 二氧化碳 、 NADH 、 5α-cholestadien-(8.24)-one-(3)
  参考文献：
  名称：

  The gene mutated in bare patches and striated mice encodes a novel 3β-hydroxysteroid dehydrogenase

  摘要：

  人类和小鼠中都有X连锁显性遗传病，这种病在单倍体雄性中仅在产前致死，1。但在这两种物种中，都没有分离出相关的基因。裸斑（Bpa）和条纹（Str）小鼠突变最初是在X射线照射雄性小鼠的雌性后代中发现的2,3。随后，又发现了其他独立等位基因。我们之前将这些X连锁显性、雄性致死突变定位到与人类Xq28同源的600kb重叠区域（参考文献4），并在此区间内确定了几个候选基因5。在此，我们报告了其中一种基因Nsdhl的突变，该基因编码一种NAD（P）H类固醇脱氢酶样蛋白，在两个独立的Bpa和三个独立的Str等位基因中都有突变。对患病Bpa小鼠组织中的固醇进行定量分析，证实了Nsdhl在胆固醇生物合成中的作用。我们的研究结果表明，Bpa和Str是等位基因突变，并确定了第一个与X连锁显性、雄性致死表型相关的哺乳动物基因座。它们还扩展了与胆固醇代谢异常相关的表型谱。

  DOI：

  10.1038/9700
• 作为产物：
  描述：

  (4alpha,5alpha,10Xi,13Xi,14Xi,17Xi,20Xi)-4-甲基胆甾-8,24-二烯-3-醇 、 铁燧石 、 氢(+1)阳离子 、 氧气 生成 4alpha-Carboxyzymosterol(1-) 、 铁阳离子 、 水
  参考文献：
  名称：

  哺乳动物胆固醇生物合成途径的全面机器可读视图。

  摘要：

  胆固醇生物合成是健康和疾病中众多生物过程的中心代谢中心。现有文献中缺乏对胆固醇通路如何构建以及它如何与其他通路系统相互作用的详细、综合的单一视图描述。在这里，我们对现有文献进行了系统回顾，并提供了详细的途径图，描述了胆固醇生物合成途径（甲羟戊酸、Kandutch-Russell 和 Bloch 途径）和导致 24(S),25-环氧胆固醇合成的分流途径. 该图是使用系统生物学图形符号 (SBGN) 生成的，并以 SBGN-ML 格式提供，这是一种人类可读且机器语义可解析的开放社区文件格式。

  DOI：

  10.1016/j.bcp.2013.03.021

文献信息

• Interactions of the ergosterol biosynthetic pathway with other lipid pathways
  作者：C. Lang、M. Veen

  DOI：10.1042/bst20051178

  日期：2005.10.1

  Micro-organisms have recently received broad attention as sources of novel lipids. An increased understanding of the effects of fats and oils and their composition on the metabolism and on health has shifted the focus towards the use of lipids for disease treatment and prevention and for the promotion of good health. A large range of lipidic products produced by yeast is known today. Ergosterol and its metabolic precursors are major lipidic components of industrial and commercial interest. Having in mind the aim to increase the productivity of ergosterol and its precursor metabolites, both the knowledge of regulatory mechanisms of the biosynthetic pathway and its interactions with other lipid pathways like those of sphingolipids, phospholipids and fatty acids are crucial.
• Rahimtula A.D.; Gaylor J.L., J Biol Chem, 1972, 0021-9258, 9-15
  作者：Rahimtula A.D.、Gaylor J.L.

  DOI：——

  日期：——
• Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay
  作者：Miao He、Lisa E. Kratz、Joshua J. Michel、Abbe N. Vallejo、Laura Ferris、Richard I. Kelley、Jacqueline J. Hoover、Drazen Jukic、K. Michael Gibson、Lynne A. Wolfe、Dhanya Ramachandran、Michael E. Zwick、Jerry Vockley

  DOI：10.1172/jci42650

  日期：2011.3.1

  Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase-like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors alpha and beta (LXR alpha and LXR beta), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined.
• Miller W.L.; Gaylor J.L., J Biol Chem, 1970, 0021-9258, 5375-81
  作者：Miller W.L.、Gaylor J.L.

  DOI：——

  日期：——