Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition.
Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition.
复制标题
DOI：
10.1186/1475-2875-11-337
复制
发表时间：
2012-10-08
期刊：
影响因子：
3
通讯作者：
Egan TJ
中科院分区：
文献类型：
--
作者：
Ambele MA;Egan TJ
疟疾寄生虫通过与中性脂质密切结合转化为结晶的疟原虫色素来处理宿主来源的铁血红素（铁（III）原卟啉IX，Fe（III）PPIX）。脂质非常有效地介导合成的血色素（β-血红素）的形成。然而，脂质，Fe（III）PPIX和生理相关的离子和生物分子的浓度对反应速率的影响是未知的。在水性介质（pH 4.8，37 ° C）中制备含有Fe（III）PPIX的脂肪乳剂以介导β-血红素形成。在不同时间淬灭反应，并以比色法测量游离Fe（III）PPIX作为吡啶络合物，并分析动力学和产率。用FTIR、TEM和电子衍射对产物进行了表征。还使用自发荧光通过共聚焦显微镜监测β-正铁血红素的形成。在固定的Fe（III）PPIX浓度下，β-血红素产率随着脂质浓度的降低而保持恒定，直到达到截止比，此时效率急剧下降。对于与疟原虫色素相关的中性脂质混合物（NLB）和棕榈酰甘油（MPG），这发生在低于0.54的脂质/Fe（III）PPIX（L/H）比时。发现速率常数随着L/H比高于截止值而增加。在16 μ M MPG下，Fe（III）PPIX浓度可以升高，直到L/H比达到相同的比例，然后观察到产率突然下降。MPG介导的β-血红素形成对生物相关阳离子（Na+、K+、Mg2+、Ca2+）或阴离子（H2PO4 −、HCO3 −、ATP、2，3-二磷酸甘油酸盐、谷胱甘肽）相对不敏感。共聚焦显微镜显示β-血红素形成与脂质颗粒相关。β-血红素形成的动力学表明，在离子浓度的生理现实条件下，单独的血红蛋白相关中性脂质能够以足够的速率介导β-血红素形成，以解释血红蛋白的形成。
The malaria parasite disposes of host-derived ferrihaem (iron(III)protoporphyrin IX, Fe(III)PPIX) by conversion to crystalline haemozoin in close association with neutral lipids. Lipids mediate synthetic haemozoin (β-haematin) formation very efficiently. However, the effect on reaction rates of concentrations of lipid, Fe(III)PPIX and physiologically relevant ions and biomolecules are unknown. Lipid emulsions containing Fe(III)PPIX were prepared in aqueous medium (pH 4.8, 37°C) to mediate β-haematin formation. The reaction was quenched at various times and free Fe(III)PPIX measured colorimetrically as a pyridine complex and the kinetics and yields analysed. Products were also characterized by FTIR, TEM and electron diffraction. Autofluorescence was also used to monitor β-haematin formation by confocal microscopy. At fixed Fe(III)PPIX concentration, β-haematin yields remained constant with decreasing lipid concentration until a cut-off ratio was reached whereupon efficiency decreased dramatically. For the haemozoin-associated neutral lipid blend (NLB) and monopalmitoylglycerol (MPG), this occurred below a lipid/Fe(III)PPIX (L/H) ratio of 0.54. Rate constants were found to increase with L/H ratio above the cut-off. At 16 μM MPG, Fe(III)PPIX concentration could be raised until the L/H ratio reached the same ratio before a sudden decline in yield was observed. MPG-mediated β-haematin formation was relatively insensitive to biologically relevant cations (Na+, K+, Mg2+, Ca2+), or anions (H2PO4−, HCO3−, ATP, 2,3-diphosphoglycerate, glutathione). Confocal microscopy demonstrated β-haematin formation occurs in association with the lipid particles. Kinetics of β-haematin formation have shown that haemozoin-associated neutral lipids alone are capable of mediating β-haematin formation at adequate rates under physiologically realistic conditions of ion concentrations to account for haemozoin formation.
登录
查看更多内容
影响因子：
2.9
作者：
Ncokazi, KK;Egan, TJ
通讯作者：
Egan, TJ
影响因子：
4.3
作者：
Mauritz JM;Esposito A;Ginsburg H;Kaminski CF;Tiffert T;Lew VL
通讯作者：
Lew VL
DOI：
10.1039/b914359a
发表时间：
2010-02-07
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Hoang AN;Ncokazi KK;de Villiers KA;Wright DW;Egan TJ
通讯作者：
Egan TJ
影响因子：
3.5
作者：
Egan, Timothy J.;Chen, Jeff Y-J.;Wood, Bayden R.
通讯作者：
Wood, Bayden R.
影响因子：
3.5
作者：
Oliveira, MF;Kycia, SW;Ferreira, ST
通讯作者：
Ferreira, ST