negative regulation of ATP citrate synthase activity

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of ATP citrate synthase activity. [GOC:BHF]

Negative regulation of ATP citrate synthase activity is a crucial process that modulates the production of citrate, a key intermediate in both energy metabolism and biosynthesis. ATP citrate lyase, also known as ATP-citrate synthase, catalyzes the reversible conversion of citrate to oxaloacetate and acetyl-CoA. This reaction plays a central role in various metabolic pathways, including the citric acid cycle, fatty acid biosynthesis, and gluconeogenesis.

The activity of ATP citrate lyase is tightly regulated to ensure proper balance and coordination within the metabolic network. Negative regulation of this enzyme involves several mechanisms that aim to suppress its activity under specific physiological conditions. These mechanisms include:

1. **Product Inhibition:** Citrate itself acts as a competitive inhibitor of ATP citrate lyase. As citrate levels rise, it directly competes with the substrate, preventing the enzyme from binding and catalyzing the reaction. This feedback mechanism helps to maintain optimal levels of citrate within the cell.

2. **Allosteric Regulation:** ATP citrate lyase is subject to allosteric regulation by various metabolites, including ATP, ADP, and long-chain fatty acids. ATP, a product of energy production, inhibits the enzyme, while ADP, a sign of low energy levels, activates it. Long-chain fatty acids also act as inhibitors, likely reflecting the role of ATP citrate lyase in fatty acid biosynthesis.

3. **Phosphorylation:** ATP citrate lyase can be phosphorylated by protein kinases, leading to a decrease in its activity. This phosphorylation event often occurs in response to signals that indicate a need to reduce citrate production, such as high glucose levels or the presence of excess fatty acids.

4. **Transcriptional Regulation:** The expression of ATP citrate lyase can be regulated at the level of gene transcription. Factors that influence the transcription of the gene encoding ATP citrate lyase include hormonal signals, nutritional status, and cellular energy demands.

5. **Protein Degradation:** ATP citrate lyase can be degraded by proteasomes, a process that eliminates damaged or unwanted proteins. This degradation pathway plays a role in controlling the overall amount of enzyme present in the cell.

In summary, negative regulation of ATP citrate synthase activity is a complex process involving multiple mechanisms. These mechanisms collectively ensure that the activity of this key enzyme is tightly controlled in response to changing metabolic needs and physiological conditions. By modulating citrate production, negative regulation contributes to maintaining metabolic homeostasis and supporting diverse cellular functions.'
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Proteins (1)

Compounds (6)