NMR Investigations of Cellular Energy Metabolism
NMR Investigations of Cellular Energy Metabolism
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细胞能量代谢的核磁共振研究
DOI：
--
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发表时间：
1987
影响因子：
5.2
通讯作者：
L. Katz
中科院分区：
文献类型：
--
作者：
R. Balaban;A. Koretsky;L. Katz
调节细胞内能量代谢的机制还不完全清楚。多年来，人们已经确定，组织，如心脏和肾脏，可以平衡它们的能量转换率与功输出。然而，导致这些过程协调的实际细胞内通信网络仍然是一个活跃的辩论和研究领域。在过去的几年里，我们一直专注于通过改变许多组织的功输出来调节线粒体内的氧化磷酸化，并观察对这一挑战的生化反应。由于氧化磷酸化是大多数细胞中化学能（即三磷酸腺苷（ATP））的主要来源，因此了解该过程的控制是全面理解细胞能量利用的关键。对分离线粒体的早期研究导致了这样一种观点，即由于产生ATP酶的工作引起ATP水解的变化，细胞质ADP或P1水平的改变负责氧化磷酸化的适当调节。~ *“这些磷酸盐控制呼吸的部位被认为是一个简单的Michaelis-Menten型底物，由ADP和P控制。9或磷酸化电位和线粒体氧化还原之间存在接近平衡的关系。所有上述关于磷酸盐的模型表明，如果腺苷酸磷酸盐和P的变化负责所观察到的呼吸的“反馈”控制，则在组织的功输出改变期间应观察到它们的变化。例如，早期6和最近关于ADP在分离的线粒体中控制呼吸的工作证明了线粒体外ADP和呼吸之间的可饱和Michaelis-Menten型关系。ADP的表观亲和力约为20-LM，这与许多活性组织中计算的ADP值接近。12此处有趣的是ADP与呼吸之间的关系的斜率从不大于1：1。也就是说，ADP增加50%会导致ADP呼吸增加50%。因此，如果这种简单的机制是负责呼吸控制在完整的细胞，50%的工作或呼吸增加，应伴随着50%的增加胞质ADP。相对较新的证据表明，“P N M R "可用于跟踪v ~ v O"~中的高能磷酸盐含量以及这些化合物的周转，这允许重新研究这些磷酸盐在体内呼吸调节中的作用。作为一种非破坏性技术，每个组织都可以作为自己的对照，而不会受到这些快速代谢底物发生的冷冻钳伪影的困扰。几项使用“P N M R "的研究直接或间接地研究了高能磷酸盐与许多组织中的功输出之间的关系。最初的动物P N M R研究表明，在骨骼肌中，
The mechanism for the regulation of energy metabolism within the cell is not entirely understood. For many years it has been established that tissues, such as heart'-' and kidney,4*' can balance their rate of energy conversion with work output. However, the actual intracellular communication network that results in the coordination of these processes is still an area of active debate and research. Over the last several years we have been concentrating on the regulation of oxidative phosphorylation within the mitochondria by changes in work output in numerous tissues and observing the biochemical response to this challenge. Since oxidative phosphorylation is a major source of chemical energy (i.e. adenosine triphosphate (ATP)) in most cells, an understanding of the control of this process is key to an overall comprehension of energy utilization by the cell. Early work on isolated mitochondria led to the notion that alterations in cytoplasmic ADP or P, levels, due to changes in ATP hydrolysis by the work producing ATPases, are responsible for the appropriate regulation of oxidative phosphorylat i ~ n . ~ * ' The site of respiratory control by these phosphates has been suggested to be a simple Michaelis-Menten type substrate control by ADP and P,?9 or a near equilibrium relation existed between the phosphorylation potential and the mitochondria redox All of the above models concerning phosphates suggest that changes in the adenylate phosphates and P, should be observed during alterations in work output by a tissue if they are responsible for the observed "feedback" control of respiration. For example, the early6 and most recent work on the control of respiration by ADP in isolated mitochondria demonstrated a saturable Michaelis-Menten type relationship between extramitochondrial ADP and respiration. The apparent affinity of ADP is approximately 20 ~LM, which is close to the calculated ADP value in many active tissues.12 Of interest here is that the slope of the relationship between ADP and respiration is never greater than 1 : 1. That is, a 50% increase in ADP results in a 50% increase in respiration near the mitochondria1 K , for ADP. Therefore, if this simple mechanism is responsible for respiratory control in the intact cell, a 50% increase in work or respiration should be accompanied by a 50% increase in cytosolic ADP. The relatively recent demonstration that "P N M R can be used to follow high energy phosphate contents in v ~ v o ' ~ ' ~ as well as the turnover of these compound^,'^ has permitted the reinvestigation of the role of these phosphates in the regulation of in vivo respiration. As a non-destructive technique, each tissue can serve as its own control and not be plagued by freeze-clamp artifacts occurring with these rapidly metabolized substrates. Several studies using "P N M R have investigated either directly or indirectly the relationship between high energy phosphates and work output in numerous tissues. The initial "P N M R studies in animals demonstrated that in skeletal muscle the high
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磷核磁共振观察大鼠腿部肌肉的化学变化。
DOI：
10.1152/ajpcell.1985.248.5.c542
发表时间：
1985
期刊：
The American journal of physiology
影响因子：
--
作者：
Kushmerick,MJ;Meyer,RA
通讯作者：
Meyer,RA
31P-NMR 研究正性肌力药物肾上腺素和哇巴因以及离子载体 R02-2985 (X537A) 在离体灌注大鼠心脏中的一些代谢和功能影响。
DOI：
10.1016/0167-4889(82)90008-8
发表时间：
1982
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Matthews,PM;Williams,SR;Seymour,AM;Schwartz,A;Dube,G;Gadian,DG;Radda,GK
通讯作者：
Radda,GK
离体大鼠心脏中肌酸激酶和 ATP 合成的反应率。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bittl,JA;Ingwall,JS
通讯作者：
Ingwall,JS
影响因子：
56.9
作者：
BALABAN, RS;KANTOR, HL;BRIGGS, RW
通讯作者：
BRIGGS, RW
DOI：
10.1016/s0021-9258(18)34936-6
发表时间：
1982-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
W E Jacobus;R W Moreadith;K M Vandegaer
通讯作者：
W E Jacobus;R W Moreadith;K M Vandegaer