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How does the enzyme phosphofructokinase regulate the rates of glycolysis and gluconeogenesis in the liver cells?

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Phosphofructokinase  PFK  is a key regulatory enzyme in the glycolysis pathway, which is responsible for the breakdown of glucose to produce energy in the form of ATP. In liver cells, PFK plays a crucial role in regulating the rates of glycolysis and gluconeogenesis, ensuring that the balance between glucose breakdown and synthesis is maintained.PFK catalyzes the conversion of fructose-6-phosphate  F6P  to fructose-1,6-bisphosphate  F1,6BP  in the glycolysis pathway. This reaction is considered the first committed step in glycolysis, as it is irreversible and commits the glucose molecule to be further metabolized in the glycolytic pathway.The regulation of PFK activity is achieved through several mechanisms, including allosteric regulation, covalent modification, and transcriptional regulation.1. Allosteric regulation: PFK is allosterically regulated by various metabolites that act as effectors. High levels of ATP, an indicator of high cellular energy status, inhibit PFK activity, thus slowing down glycolysis. Conversely, AMP, which indicates low energy levels, activates PFK, promoting glycolysis. Additionally, citrate, a key intermediate in the citric acid cycle, also inhibits PFK, indicating that the cell has sufficient energy and does not need to break down more glucose.2. Covalent modification: PFK can be regulated by covalent modification, such as phosphorylation. In liver cells, glucagon, a hormone that promotes gluconeogenesis, activates protein kinase A  PKA , which in turn phosphorylates and inhibits PFK-2. This leads to a decrease in the production of fructose-2,6-bisphosphate  F2,6BP , a potent activator of PFK-1. As a result, glycolysis is inhibited, and gluconeogenesis is favored.3. Transcriptional regulation: The expression of PFK can be regulated at the transcriptional level. For example, insulin, a hormone that promotes glucose uptake and glycolysis, can increase the expression of PFK, while glucagon can decrease its expression.In summary, the enzyme phosphofructokinase plays a crucial role in regulating the rates of glycolysis and gluconeogenesis in liver cells. It does so through allosteric regulation, covalent modification, and transcriptional regulation, ensuring that the balance between glucose breakdown and synthesis is maintained according to the cell's energy needs.
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