You are running a 100 km ultramarathon. At around 50 km into the race, you have depleted your glycogen stores but are still running aerobically. Fatty acid oxidation, the citric acid cycle and the electron transport chain are the main metabolic processes occurring. What product of fatty acid oxidation would inhibit glycolysis?
This happens through Randle cycle. Randle cycle refers to the significant reduction in the uptake and utilization of glucose that occurs in the muscle when fatty acid oxidation is intense. This phenomenon is explained as follows: the oxidation of fatty acids yields acetyl-CoA from which citrate is generated by the action of citrate synthase via Kreb`s cycle. High values of acetyl-CoA/CoA and NADH/NAD+ ratios stimulate pyruvate dehydrogenase kinase, which phosphorylates and inactivates PDH. ATP and citrate inhibit phosphofructokinase, with the accumulation of substrates from previous stages, including G-6-P, which has an inhibitory effect on hexokinase. This depresses glycolysis.
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