Yarian Connie S, Toroser Dikran, Sohal Rajindar S
Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Mech Ageing Dev. 2006 Jan;127(1):79-84. doi: 10.1016/j.mad.2005.09.028. Epub 2005 Nov 10.
The activities of the citric acid cycle enzymes were determined in mitochondria isolated from kidneys of relatively young, middle age, and old mice. Aconitase exhibited the most significant decrease in activity with age. The activity of alpha-ketoglutarate dehydrogenase exhibited a modest decrease in activity, while NADP(+)-isocitrate dehydrogenase (NADP(+)-ICD) activity increased moderately with age. Activities of citrate synthase, NAD(+)-isocitrate dehydrogenase (NAD(+)-ICD), succinyl-CoA synthetase (SCS), succinate dehydrogenase (SD), fumarase (FUM), and malate dehydrogenase (MD) were not affected. The molar ratio of the intra-mitochondrial redox indicator, NADPH:NADP(+), was higher in young compared to old animals, while the NADH:NAD(+) molar ratio remained unchanged. It is suggested that an age-related decrease in aconitase activity along with relatively subtle alterations in activities of some other citric acid cycle enzymes are likely to contribute to a decline in the overall efficiency of mitochondrial bioenergetics. The biological consequences of such alterations include age-related fluctuations in the citric acid cycle intermediates, which are precursors of protein synthesis, activators of fatty acid synthesis, and can also act as ligands for orphan G-protein coupled receptors.
在从相对年轻、中年和老年小鼠的肾脏中分离出的线粒体中，测定了柠檬酸循环酶的活性。乌头酸酶的活性随年龄增长下降最为显著。α-酮戊二酸脱氢酶的活性有适度下降，而NADP(+)-异柠檬酸脱氢酶（NADP(+)-ICD）的活性随年龄适度增加。柠檬酸合酶、NAD(+)-异柠檬酸脱氢酶（NAD(+)-ICD）、琥珀酰辅酶A合成酶（SCS）、琥珀酸脱氢酶（SD）、延胡索酸酶（FUM）和苹果酸脱氢酶（MD）的活性未受影响。与老年动物相比，年轻动物线粒体内氧化还原指示剂NADPH:NADP(+)的摩尔比更高，而NADH:NAD(+)摩尔比保持不变。有人提出，乌头酸酶活性随年龄下降以及其他一些柠檬酸循环酶活性相对细微的变化，可能导致线粒体生物能量学整体效率下降。这些变化的生物学后果包括柠檬酸循环中间产物随年龄的波动，这些中间产物是蛋白质合成的前体、脂肪酸合成的激活剂，还可作为孤儿G蛋白偶联受体的配体。
