HUMAN LIVER LONG-CHAIN 3-HYDROXYACYL-COENZYME-A DEHYDROGENASE IS A MULTIFUNCTIONAL MEMBRANE-BOUND BETA-OXIDATION ENZYME OF MITOCHONDRIA
HUMAN LIVER LONG-CHAIN 3-HYDROXYACYL-COENZYME-A DEHYDROGENASE IS A MULTIFUNCTIONAL MEMBRANE-BOUND BETA-OXIDATION ENZYME OF MITOCHONDRIA
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DOI：
10.1016/0006-291x(92)90501-b
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发表时间：
1992-03-16
影响因子：
3.1
通讯作者：
MIDDLETON, B
中科院分区：
文献类型：
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作者：
CARPENTER, K;POLLITT, RJ;MIDDLETON, B
我们已经纯化到同质的长链特异性3-羟酰辅酶A脱氢酶从线粒体膜的人类婴儿肝脏。该酶由230 kDa的天然结构内的71 kDa和47 kDa的不相同亚基组成。纯酶对3-酮己酰-CoA有活性，对C10至C16酰基链长度的3-酮酰-CoA底物有最大活性，但对乙酰乙酰-CoA无活性。除了3-羟酰-CoA脱氢酶活性外，该酶还具有2-烯酰-CoA水合酶和3-酮酰-CoA硫解酶活性，这些活性不能与脱氢酶分离。这些酶都没有表现出与C4底物的活性，但所有的活性与C6和更长的酰基链长度的底物。因此，它们不同于先前描述的任何。这种人肝线粒体膜结合酶催化中链和长链2-烯酰-CoA化合物转化为：1）在单独NAD存在下转化为3-酮酰-CoA，2）在NAD和CoASH存在下转化为乙酰-CoA（加上相应的酰基-CoA衍生物）。因此，它是一种多功能酶，类似于E.大肠杆菌，但其独特的膜定位和底物特异性。我们认为，它的存在解释了多次未能检测到任何线粒体β-氧化的中间体。
We have purified to homogeneity the long-chain specific 3-hydroxyacyl-CoA dehydrogenase from mitochondrial membranes of human infant liver. The enzyme is composed of non-identical subunits of 71kDa and 47kDa within a native structure of 230kDa. The pure enzyme is active with 3-ketohexanoyl-CoA and gives maximum activity with 3-ketoacyl-CoA substrates of C10to C16acyl-chain length but is inactive with acetoacetyl-CoA. In addition to 3-hydroxyacyl-CoA dehydrogenase activity, the enzyme possesses 2-enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities which cannot be separated from the dehydrogenase. None of these enzymes show activity with C4substrates but all are active with C6and longer acyl-chain length substrates. They are thus distinct from any described previously. This human liver mitochondrial membrane-bound enzyme catalyses the conversion of medium- and long-chain 2-enoyl-CoA compounds to: 1) 3-ketoacyl-CoA in the presence of NAD alone and 2) to acetyl-CoA (plus the corresponding acyl-CoA derivatives) in the presence of NAD and CoASH. It is therefore a multifunctional enzyme, resembling the beta-oxidation enzyme ofE. coli, but unique in its membrane location and substrate specificity. We propose that its existence explains the repeated failure to detect any intermediates of mitochondrial beta-oxidation.