Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal alpha-methylacyl-CoA racemase deficiency.
Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal alpha-methylacyl-CoA racemase deficiency.
复制标题
过氧化物酶体 α-甲基酰基辅酶 A 消旋酶缺乏症中二羟基胆甾烷酸和三羟基胆甾烷酸非对映异构体的血浆分析。
作者：
S. Ferdinandusse;H. Overmars;S. Denis;H. Waterham;R. Wanders;P. Vreken
我们发现了一种新的过氧化物酶体疾病，是由α -甲基酰基辅酶a （CoA）消旋酶缺乏引起的。患有这种疾病的患者血浆中胆汁酸中间体二羟基和三羟基胆甾酸（DHCA和THCA）水平升高，这些都是过氧化物酶体β -氧化系统的底物。α -甲基酰基辅酶a消旋酶在支链脂肪酸和脂肪酸衍生物的β -氧化过程中起重要作用，因为它能催化几种(2R)-甲基支链脂肪酸酰基辅酶a转化为它们的(2S)-异构体。只有2-甲基为(S)构型的立体异构体才能通过β -氧化降解。在这项研究中，我们使用液相色谱/串联质谱（LC-MS/MS）分析了积累在α -甲基酰基辅酶a消消酶缺乏患者血浆中的胆汁酸中间体，并比较了齐薇格综合征患者和胆汁淤积性肝病患者血浆中的胆汁酸中间体。我们发现消消酶缺乏的患者只积累游离的和牛磺酸结合的DHCA和THCA的(R)-异构体，而齐薇格综合征患者和胆汁淤积性肝病患者的血浆中两种异构体都存在。在这些结果的基础上，我们描述了一种简单可靠的诊断血浆分析α -甲基酰基辅酶a消旋酶缺陷患者的方法。我们的研究结果还表明-甲基辅酶a消旋酶在胆汁酸形成中起着独特的作用。——费迪南多斯，S.， H.欧弗马斯，S.丹尼斯，H. R.沃特汉姆，R. J. A.万德斯和P.弗瑞肯。过氧化物酶体-甲基酰基辅酶a消旋酶缺乏症中二羟基和三羟基胆甾酸非对映异构体的血浆分析。[j] .油脂杂志。2001。42: 137; -141年。
We identified a new peroxisomal disorder caused by a deficiency of the enzyme alpha-methylacyl-coenzyme A (CoA) racemase. Patients with this disorder show elevated plasma levels of pristanic acid and the bile acid intermediates di- and trihydroxycholestanoic acid (DHCA and THCA), which are all substrates for the peroxisomal beta-oxidation system. alpha-Methylacyl-CoA racemase plays an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives because it catalyzes the conversion of several (2R)-methyl-branched-chain fatty acyl-CoAs to their (2S)-isomers. Only stereoisomers with the 2-methyl group in the (S)-configuration can be degraded via beta-oxidation. In this study we used liquid chromatography/tandem mass spectrometry (LC-MS/MS) to analyze the bile acid intermediates that accumulate in plasma from patients with a deficiency of alpha-methylacyl-CoA racemase and, for comparison, in plasma from patients with Zellweger syndrome and patients with cholestatic liver disease.We found that racemase-deficient patients accumulate exclusively the (R)-isomer of free and taurine-conjugated DHCA and THCA, whereas in plasma of patients with Zellweger syndrome and patients with cholestatic liver disease both isomers were present. On the basis of these results we describe an easy and reliable method for the diagnosis of alpha-methylacyl-CoA racemase-deficient patients by plasma analysis. Our results also show that alpha-methylacyl-CoA racemase plays a unique role in bile acid formation. - Ferdinandusse, S., H. Overmars, S. Denis, H. R. Waterham, R. J. A. Wanders, and P. Vreken. Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal alpha-methylacyl-CoA racemase deficiency. J. Lipid Res. 2001. 42: 137;-141.
从人胆汁中分离出的 3 α、7 α、12 α-三羟基-5 β-胆甾坦-26-油酸中 C-25 的构型。
影响因子：
6.5
作者：
Batta,AK;Salen,G;Shefer,S;Dayal,B;Tint,GS
通讯作者：
Tint,GS