在代谢中起关键作用的多种线粒体基质酶需要辅因子来发挥作用。由于线粒体内膜的高度不通透性,这些辅因子需要在线粒体内合成或导入,他们自己或他们的前体之一,进入细胞器。已确定属于线粒体载体蛋白质家族的转运蛋白可转运辅酶:焦磷酸硫胺素,辅酶A,FAD和NAD+,它们在结构上都与核苷酸相似,来自不同的B族维生素。这些线粒体辅因子或多或少紧密地与它们的酶结合,在参与特定的反应步骤后,再生,自发或通过其他酶,回到他们的活跃状态,为下一轮催化做好准备。线粒体辅因子载体基因中的致病突变不仅损害了运输反应,而且损害了使用该特定辅因子的所有线粒体酶的活性以及其中涉及辅因子依赖性酶的代谢途径。线粒体运输,代谢和疾病的辅因子硫胺素焦磷酸,辅酶A,FAD和NAD+是本综述的重点。
Multiple mitochondrial matrix enzymes playing key roles in metabolism require cofactors for their action. Due to the high impermeability of the mitochondrial inner membrane, these cofactors need to be synthesized within the mitochondria or be imported, themselves or one of their precursors, into the organelles. Transporters belonging to the protein family of mitochondrial carriers have been identified to transport the coenzymes: thiamine pyrophosphate,
coenzyme A, FAD and NAD+ , which are all structurally similar to nucleotides and derived from different B-vitamins. These mitochondrial cofactors bind more or less tightly to their enzymes and, after having been involved in a specific reaction step, are regenerated, spontaneously or by other enzymes, to return to their active form, ready for the next catalysis round. Disease-causing mutations in the mitochondrial cofactor carrier genes compromise not only the transport reaction but also the activity of all mitochondrial enzymes using that particular cofactor and the metabolic pathways in which the cofactor-dependent enzymes are involved. The mitochondrial transport, metabolism and diseases of the cofactors thiamine pyrophosphate,
coenzyme A, FAD and NAD+ are the focus of this
review.