Cori cycle

The Cori cycle (also known as the Lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate. Muscular activity requires ATP, which is provided by the breakdown of glycogen in the skeletal muscles. The breakdown of glycogen, a process known as glycogenolysis, releases glucose in the form of glucose-1-phosphate (G-1-P). The G-1-P is converted to G-6-P by the enzyme phosphoglucomutase. G-6-P is readily fed into glycolysis, (or can go into the pentose phosphate pathway if G-6-P concentration is high) a process that provides ATP to the muscle cells as an energy source. During muscular activity, the store of ATP needs to be constantly replenished. When the supply of oxygen is sufficient, this energy comes from feeding pyruvate, one product of glycolysis, into the Krebs cycle. When oxygen supply is insufficient, typically during intense muscular activity, energy must be released through anaerobic metabolism. Lactic acid fermentation converts pyruvate to lactate by lactate dehydrogenase. Most importantly, fermentation regenerates NAD+, maintaining the NAD+ concentration so that additional glycolysis reactions can occur. The fermentation step oxidizes the NADH produced by glycolysis back to NAD+, transferring two electrons from NADH to reduce pyruvate into lactate. Instead of accumulating inside the muscle cells, lactate produced by anaerobic fermentation is taken up by the liver. This initiates the other half of the Cori cycle. In the liver, gluconeogenesis occurs. From an intuitive perspective, gluconeogenesis reverses both glycolysis and fermentation by converting lactate first into pyruvate, and finally back to glucose. The glucose is then supplied to the muscles through the bloodstream; it is ready to be fed into further glycolysis reactions. If muscle activity has stopped, the glucose is used to replenish the supplies of glycogen through glycogenesis. Overall, the glycolysis part of the cycle produces 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis part. Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules indicates that the Cori cycle shifts the metabolic burden from the muscles to the liver. Source: [https://en.wikipedia.org/wiki/Cori_cycle Wikipedia] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1946 CPTAC Assay Portal]

柯里循环（亦称乳酸酸循环），得名于其发现者卡尔·费迪南德·柯里和格蒂·柯里，指的是一种代谢途径。在该途径中，由肌肉中无氧糖酵解产生的乳酸转移至肝脏，并转化为葡萄糖。葡萄糖随后返回肌肉，再被代谢回乳酸。肌肉活动需要三磷酸腺苷（ATP），而骨骼肌中糖原的分解即为提供ATP的途径。糖原分解，即糖原解作用，以葡萄糖-1-磷酸（G-1-P）的形式释放葡萄糖。G-1-P在磷酸葡萄糖异构酶的催化下转化为G-6-P。G-6-P随即进入糖酵解过程，或在高浓度时进入戊糖磷酸途径，这一过程为肌肉细胞提供ATP作为能量来源。在肌肉活动期间，ATP的储存需要不断得到补充。当氧气供应充足时，这种能量来源于将糖酵解的产物丙酮酸输入三羧酸循环。当氧气供应不足，通常在剧烈的肌肉活动中，能量必须通过无氧代谢释放。乳酸发酵通过乳酸脱氢酶将丙酮酸转化为乳酸。最重要的是，发酵过程再生NAD+，维持NAD+浓度，以便额外的糖酵解反应得以进行。发酵步骤将糖酵解产生的NADH氧化回NAD+，从NADH中转移两个电子，将丙酮酸还原为乳酸。由无氧发酵产生的乳酸不会在肌肉细胞内积累，而是被肝脏摄取。这启动了柯里循环的另一部分。在肝脏中，发生糖异生作用。从直观的角度来看，糖异生通过先将乳酸转化为丙酮酸，最终再转化为葡萄糖，逆转了糖酵解和发酵过程。葡萄糖随后通过血液循环供应给肌肉；它准备进入进一步的糖酵解反应。如果肌肉活动停止，葡萄糖则用于通过糖原合成补充糖原储备。总体而言，循环的糖酵解部分产生2个ATP分子，而糖异生部分消耗6个ATP分子。每个循环迭代都需要净消耗4个ATP分子。因此，该循环不能无限期地持续进行。ATP分子的密集消耗表明，柯里循环将代谢负担从肌肉转移到肝脏。来源：[https://en.wikipedia.org/wiki/Cori_cycle Wikipedia]。该途径上的蛋白质有靶向检测方法，可通过[https://assays.cancer.gov/available_assays?wp_id=WP1946 CPTAC检测门户]获得。