Inhibition of citrulline synthesis by octanoate and its modulation by adenine nucleotides

W.H. Lutz , T.P. Geisbuhler , J.D. Pollack , H.J. McClung , A.J. Merola
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引用次数: 3

Abstract

Liver mitochondria from octanoate-treated rabbits showed an impaired ability to synthesize citrulline. Two methods were used to evaluate citrulline synthesis in rat liver mitochondria. Under these conditions octanoate inhibited citrulline synthesis by over 50%. When ATP was included in the assay medium the inhibitory effect of ocatanoate was prevented. In the absence of ATP in the suspending medium, octanoate did not significantly lower total adenine nucleotides in rat liver mitochondria. However, under these conditions octanoate caused a change in the adenine nucleotide profile such that ATP content was decreased and AMP content was increased. When ATP was present in the assay medium, octanoate caused a similar increase in AMP content. However, ATP decreased only slightly. The alterations in mitochondrial adenine nucleotide profile by octanoate and the reversal of the effect by exogenous ATP suggests that octanoate inhibits citrulline synthesis via reduced intramitochondrial ATP levels. The ability of octanoate to lower mitochondrial ATP and elevate mitochondrial AMP may be related to its intramitochondrial activation by the medium chain fatty acid activating enzyme.

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辛酸对瓜氨酸合成的抑制及腺嘌呤核苷酸的调节作用
辛酸处理的家兔肝脏线粒体合成瓜氨酸的能力受损。采用两种方法评价大鼠肝脏线粒体中瓜氨酸的合成。在这些条件下辛酸抑制瓜氨酸合成超过50%。当实验培养基中加入ATP时,辛酸盐的抑制作用被阻止。在悬浮培养基中没有ATP的情况下,辛酸盐没有显著降低大鼠肝脏线粒体中的总腺嘌呤核苷酸。然而,在这些条件下辛酸引起腺嘌呤核苷酸谱的变化,使ATP含量降低,AMP含量增加。当实验培养基中存在ATP时,辛酸盐引起AMP含量的类似增加。然而,ATP仅略有下降。辛酸盐对线粒体腺嘌呤核苷酸谱的改变和外源ATP作用的逆转表明辛酸盐通过降低线粒体内ATP水平抑制瓜氨酸合成。辛酸盐降低线粒体ATP和提高线粒体AMP的能力可能与其在线粒体内被中链脂肪酸激活酶激活有关。
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