Kølvraa S, Gregersen N
Biochim Biophys Acta. 1986 May 21;876(3):515-25. doi: 10.1016/0005-2760(86)90039-1.
The degradation of medium-chained dicarboxylic (DC) acids was investigated on purified mitochondria and peroxisomes. Intact organelles were incubated with dodecanedioic acid (DC12), suberic acid (DC8) and adipic acid (DC6), and the production of lower-chained DC-acids and of acetyl-CoA + acetyl-carnitine was monitored. It was shown, that intact peroxisomes could beta-oxidize DC12, DC10, and DC8 at least as far as DC6, while intact mitochondria readily beta-oxidized DC12, and DC10 as far as succinic acid. DC8 and DC6 were not oxidized by intact mitochondria when these two acids were presented externally to the intact organelle. When they were formed intramitochondrially from DC12 and DC10, both DC8 and DC6 were, however, to a great extent beta-oxidized as far as succinic acid. The major reason for this difference between mitochondrial oxidation of externally and internally located DC8 and DC6 seems to be an inability to transport these two acids through the mitochondrial membrane. For DC12 and DC10, the mitochondrial transport systems, which were indicated to be identical to the systems used by the corresponding monocarboxylic acids, were found to be rate-limiting in the beta-oxidation of these acids. A contributing factor to the undetectable beta-oxidation of externally located DC8 and DC6 may also be, that the Km values of DC8-CoA (460 +/- 70 mumol/l) and DC6-CoA (980 +/- 90 mumol/l) towards the acyl-CoA dehydrogenases are very high. These results imply that very high concentrations of intermediates are created intramitochondrially during beta-oxidation, concentrations which are probably only formed through formation of DC8-CoA and DC6-CoA from longer DC-acids and not by transport from outside the mitochondria. The data presented thus for the first time give evidence to a pathway for medium-chained monocarboxylic acids (especially lauric acid and decanoic acid) through cytosolic omega-oxidation followed by activation, transport over the mitochondrial membrane and beta-oxidation to succinic acid.
在纯化的线粒体和过氧化物酶体上研究了中链二羧酸（DC）的降解。将完整的细胞器与十二烷二酸（DC12）、辛二酸（DC8）和己二酸（DC6）一起孵育，并监测低链DC-酸以及乙酰辅酶A+乙酰肉碱的产生。结果表明，完整的过氧化物酶体可以将DC12、DC10和DC8至少β-氧化至DC6，而完整的线粒体可以将DC12和DC10很容易地β-氧化至琥珀酸。当将DC8和DC6这两种酸从外部提供给完整的细胞器时，完整的线粒体不会氧化它们。然而，当它们在线粒体内由DC12和DC10形成时，DC8和DC6在很大程度上都会β-氧化至琥珀酸。线粒体外和线粒体内DC8和DC6的氧化存在这种差异的主要原因似乎是这两种酸无法穿过线粒体膜进行转运。对于DC12和DC10，线粒体转运系统被认为与相应一元羧酸所使用的系统相同，并且发现该转运系统是这些酸β-氧化的限速因素。线粒体外DC8和DC6无法检测到β-氧化的一个促成因素可能还在于，DC8-辅酶A（460±70μmol/L）和DC6-辅酶A（980±90μmol/L）对酰基辅酶A脱氢酶的米氏常数非常高。这些结果表明，在β-氧化过程中，线粒体内会产生非常高浓度的中间体，这些浓度可能仅通过较长链DC-酸形成DC8-辅酶A和DC6-辅酶A而产生，而不是通过从线粒体外转运形成。因此，所呈现的数据首次证明了中链一元羧酸（尤其是月桂酸和癸酸）通过胞质ω-氧化、随后活化、穿过线粒体膜转运并β-氧化为琥珀酸的途径。
