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过氧化物酶体ATP结合盒转运蛋白Pxa2在半完整酵母细胞系统中对活化脂肪酸的转运

Transport of activated fatty acids by the peroxisomal ATP-binding-cassette transporter Pxa2 in a semi-intact yeast cell system.

作者信息

Verleur N, Hettema E H, van Roermund C W, Tabak H F, Wanders R J

机构信息

Department of Clinical Chemistry, University of Amsterdam, Academic Medical Centre, The Netherlands.

出版信息

Eur J Biochem. 1997 Nov 1;249(3):657-61. doi: 10.1111/j.1432-1033.1997.00657.x.

Abstract

In the yeast Saccharomyces cerevisiae, fatty acid beta-oxidation is restricted to peroxisomes. Previous studies have shown two possible routes by which fatty acids enter the peroxisome. The first route involves transport of medium-chain fatty acids across the peroxisomal membrane as free fatty acids, followed by activation within the peroxisome by Faa2p, an acyl-CoA synthetase. The second route involves transport of long-chain fatty acids. Long-chain fatty acids enter the peroxisome via a route that involves activation in the extraperoxisomal space, followed by transport across the peroxisomal membrane. It has been suggested that this transport is dependent upon the peroxisomal ATP-binding-cassette transporters Pxa1p and Pxa2p. In this paper we investigated whether Pxa2p is directly responsible for the transport of C18:1-CoA, a long-chain acyl-CoA ester. Using protoplasts in which the plasma membrane has been selectively permeabilised by digitonin, we show that C18:1-CoA, but not C8:0-CoA, enters the peroxisome via Pxa2p, in an ATP-dependent fashion. The results obtained may contribute to the elucidation of the primary defect in the human disease X-linked adrenoleukodystrophy.

摘要

在酿酒酵母中,脂肪酸β-氧化仅限于过氧化物酶体。先前的研究表明脂肪酸进入过氧化物酶体有两种可能的途径。第一种途径涉及中链脂肪酸作为游离脂肪酸穿过过氧化物酶体膜,随后在过氧化物酶体内被酰基辅酶A合成酶Faa2p激活。第二种途径涉及长链脂肪酸的转运。长链脂肪酸通过一种途径进入过氧化物酶体,该途径包括在过氧化物酶体外空间被激活,然后穿过过氧化物酶体膜。有人提出这种转运依赖于过氧化物酶体ATP结合盒转运蛋白Pxa1p和Pxa2p。在本文中,我们研究了Pxa2p是否直接负责长链酰基辅酶A酯C18:1-CoA的转运。使用经洋地黄皂苷选择性通透质膜的原生质体,我们发现C18:1-CoA而非C8:0-CoA以ATP依赖的方式通过Pxa2p进入过氧化物酶体。所得结果可能有助于阐明人类疾病X连锁肾上腺脑白质营养不良的主要缺陷。

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