Institute of Clinical Medicine, The Faculty of Health Sciences, Aarhus University and Aarhus University Hospital, Skejby, Aarhus, Denmark.
J Inherit Metab Dis. 2010 Oct;33(5):547-53. doi: 10.1007/s10545-010-9046-1. Epub 2010 Feb 12.
In fatty acid oxidation defects, the majority of gene variations are of the missense type and, therefore, prone to inducing misfolding in the resulting mutant protein. The fate of the mutant protein depends on the nature of the gene variation and other genetic factors as well as cellular and environmental factors. Since it has been shown that certain fatty acid oxidation enzyme proteins, exemplified by mutant medium-chain and short-chain acyl-CoA dehydrogenases as well as electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase, may accumulate during cellular stress, e.g. elevated temperature, there is speculation about how such proteins may disturb the integrity of the putative fatty acid oxidation metabolone, in which the two flavoproteins link the matrix-located acyl-CoA dehydrogenases to the respiratory chain in the mitochondrial inner membrane. However, since studies so far have not been able to define the fatty acid oxidation metabolone, it is concluded that new concepts and refined techniques are required to answer these questions and thereby contribute to the elucidation of the cellular pathophysiology and the genotype-phenotype relationship in fatty acid oxidation defects.
在脂肪酸氧化缺陷中，大多数基因突变属于错义突变类型，因此容易导致突变蛋白错误折叠。突变蛋白的命运取决于基因突变的性质和其他遗传因素以及细胞和环境因素。由于已经表明，某些脂肪酸氧化酶蛋白，例如突变的中链和短链酰基辅酶 A 脱氢酶以及电子转移黄素蛋白和电子转移黄素蛋白脱氢酶，在细胞应激时可能会积累，例如，在高温下，人们推测这些蛋白质如何可能破坏假定的脂肪酸氧化代谢物的完整性，其中两种黄素蛋白将位于基质中的酰基辅酶 A 脱氢酶与线粒体内膜中的呼吸链连接起来。然而，由于迄今为止的研究还无法确定脂肪酸氧化代谢物，因此可以得出结论，需要新的概念和改进的技术来回答这些问题，从而有助于阐明脂肪酸氧化缺陷中的细胞病理生理学和基因型-表型关系。
