GLYCOLYSISGLUCONEOGENESIS-66-72.pdf

CORI CYCLE explains how glucose can be consumed by muscles, leaching lactate in the process. The liver then uses this lactate to create glucose. Muscles normally combine glucose with oxygen to generate energy. If oxygen is unavailable, the anaerobic breakdown of...

CORI CYCLE explains how glucose can be consumed by muscles, leaching lactate in the process. The liver then uses this lactate to create glucose. Muscles normally combine glucose with oxygen to generate energy. If oxygen is unavailable, the anaerobic breakdown of glucose/glycolysis/fermentation results in lactate production lactate (soluble milk acid ) excreted back into the bloodstream Gluconeogenesis (liver) maintains the proper blood sugar level through the synthesis of glucose from non-carbohydrate components. Critical to completing this loop is the catalytic co- enzyme adenosine triphosphate (ATP) Under normal oxygen, glycolysis in muscle cells produces two units of ATP and two units of pyruvate The two compounds provide the energy that enables a cell to perpetuate respiration through a series of chemical reactions called the Krebs cycle, also called the citric acid or tricarboxylic acid cycle.  liver filters the lactate out of blood to reverse engineer it to pyruvate and then into glucose. Thus, the sugar returns through the bloodstream to power the high energy demands of muscles Cori cycle is not an entirely closed loop, eg. while two ATP produced by glycolysis (muscles), it costs the liver six ATP to feed the cycle by gluconeogenesis. The physiological demands of vigorous exercise quickly engage the Cori cycle to burn and re-create glucose anaerobically. When the demand for energy exceeds the capacity of the liver to convert lactate to glucose, a condition called lactic acidosis can occur. Excess lactic acid lowers the blood pH: Damages tissue, deep hyperventilation, vomiting, and abdominal cramping. Lactic acidosis is the underlying cause of rigor mortis. With the body no longer breathing, all its muscles continue consuming glucose through uninterrupted repetition of the Cori cycle. The Cori Cycle operates during exercise. For a brief burst of ATP utilization, muscle cells utilize ~P stored as phospho-creatine. Once phospho-creatine is exhausted, ATP is provided mainly by Glycolysis, with the input coming from glycogen breakdown and from glucose uptake from the blood. (Aerobic fat metabolism, discussed elsewhere, is more significant during a lengthy period of exertion such as a marathon run.)  Cori Cycle Liver Blood Muscle Glucose Glucose 2 NAD+ 2 NAD+ 2 NADH 2 NADH 6 ~P 2 ~P 2 Pyruvate 2 Pyruvate 2 NADH 2 NADH 2 NAD+ 2 NAD+ 2 Lactate 2 Lactate Lactate produced from pyruvate passes via the blood to the liver, where it may be converted to glucose. The glucose may travel back to the muscle to fuel Glycolysis.  Cori Cycle Liver Blood Muscle Glucose Glucose 2 NAD+ 2 NAD+ 2 NADH 2 NADH 6 ~P 2 ~P 2 Pyruvate 2 Pyruvate 2 NADH 2 NADH 2 NAD+ 2 NAD+ 2 Lactate 2 Lactate The Cori cycle costs 6 ~P in liver for every 2 ~P made available in muscle. The net cost is 4 ~P. Although costly in ~P bonds, the Cori Cycle allows the organism to accommodate large fluctuations in energy requirements of skeletal muscle between rest and exercise. The equivalent of the Cori Cycle also operates during cancer. If blood vessel development does not keep pace with growth of a solid tumor, decreased O2 concentration within the tumor leads to activation of signal processes that result in a shift to anaerobic metabolism. Energy dissipation by the Cori Cycle, which expends 6 ~P in liver for every 2 ~P produced via Glycolysis for utilization within the tumor, is thought to contribute to the weight loss that typically occurs in late-stage cancer even when food intake remains normal. Cori Cycle