Kasumov Takhar, Cendrowski Andrea V, David France, Jobbins Kathryn A, Anderson Vernon E, Brunengraber Henri
Department of Nutrition, Case Western Reserve University, School of Medicine - WG 48, 10900 Euclid Avenue, Cleveland, OH 44106-4954, USA.
Arch Biochem Biophys. 2007 Jul 1;463(1):110-7. doi: 10.1016/j.abb.2007.02.022. Epub 2007 Mar 12.
Anaplerosis from propionate was investigated in rat hearts perfused with 0-2mM [(13)C(3)]propionate and physiological concentrations of glucose, lactate, and pyruvate. The data show that when the concentration of [(13)C(3)]propionate was raised from 0 to 2mM, total anaplerosis increased from 5% to 16% of the turnover of citric acid cycle intermediates. Then, [(13)C(3)]propionate abolished anaplerosis from endogenous substrates, glucose, lactate, and pyruvate. Also, while the contents of propionyl-CoA and methylmalonyl-CoA increased with [(13)C(3)]propionate concentration, the content of succinyl-CoA decreased, presumably via activation of succinyl-CoA hydrolysis by a decrease in free CoA. Under our conditions, [(13)C(3)]propionate was a purely anaplerotic substrate since there was no labeling of mitochondrial acetyl-CoA, reflected by the labeling of the acetyl moiety of citrate.
在灌注有0 - 2mM [(13)C(3)]丙酸盐以及生理浓度葡萄糖、乳酸和丙酮酸的大鼠心脏中,研究了来自丙酸盐的回补反应。数据表明,当[(13)C(3)]丙酸盐浓度从0提高到2mM时,总回补反应从柠檬酸循环中间产物周转量的5%增加到16%。然后,[(13)C(3)]丙酸盐消除了来自内源性底物(葡萄糖、乳酸和丙酮酸)的回补反应。此外,虽然丙酰辅酶A和甲基丙二酰辅酶A的含量随[(13)C(3)]丙酸盐浓度增加,但琥珀酰辅酶A的含量下降,推测是由于游离辅酶A减少激活了琥珀酰辅酶A水解。在我们的实验条件下,[(13)C(3)]丙酸盐是一种纯粹的回补底物,因为线粒体乙酰辅酶A没有标记,这通过柠檬酸乙酰部分的标记得以体现。