Concept

Futile cycle

A futile cycle, also known as a substrate cycle, occurs when two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. The reason this cycle was called "futile" cycle was because it appeared that this cycle operated with no net utility for the organism. As such, it was thought of being a quirk of the metabolism and thus named a futile cycle. After further investigation it was seen that futile cycles are very important for regulating the concentrations of metabolites. For example, if glycolysis and gluconeogenesis were to be active at the same time, glucose would be converted to pyruvate by glycolysis and then converted back to glucose by gluconeogenesis, with an overall consumption of ATP. Futile cycles may have a role in metabolic regulation, where a futile cycle would be a system oscillating between two states and very sensitive to small changes in the activity of any of the enzymes involved. The cycle does generate heat, and may be used to maintain thermal homeostasis, for example in the brown adipose tissue of young mammals, or to generate heat rapidly, for example in insect flight muscles and in hibernating animals during periodical arousal from torpor. It has been reported that the glucose metabolism substrate cycle is not a futile cycle but a regulatory process. For example, when energy is suddenly needed, ATP is replaced by AMP, a much more reactive adenine. The simultaneous carrying out of glycolysis and gluconeogenesis is an example of a futile cycle, represented by the following equation: For example, during glycolysis, fructose-6-phosphate is converted to fructose-1,6-bisphosphate in a reaction catalysed by the enzyme phosphofructokinase 1 (PFK-1). But during gluconeogenesis (i.e. synthesis of glucose from pyruvate and other compounds) the reverse reaction takes place, being catalyzed by fructose-1,6-bisphosphatase (FBPase-1). Giving an overall reaction of: That is, hydrolysis of ATP without any useful metabolic work being done.

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