How does ATP affect citrate?
Because citrate synthase is inhibited by the final product of the citric acid cycle as ATP, ADP (adenosine diphosphate) works as an allosteric activator of the enzyme as ATP is formed from ADP. Therefore, the rate of the cycle is reduced when the cell has a high level of ATP.
What is the function of ATP citrate lyase?
ATP citrate lyase functions in cancer stem cells to regulate stemness. ATP citrate lyase is important for the pyruvate citrate shuttle and lipid synthesis in insulin secretion. ACLY mRNA and protein levels markedly and quickly increase in activated macrophages.
Does citrate synthase require ATP?
Reaction. ATP citrate lyase is responsible for catalyzing the conversion of citrate and Coenzyme A (CoA) to acetyl-CoA and oxaloacetate, driven by hydrolysis of ATP.
What does citrate synthase do?
Citrate synthase catalyzes the Claisen condensation between acetyl CoA and oxaloacetate to yield, after hydrolysis of the thioester bond, citrate and CoA. This reaction probably occurs via the stabilized enolate anion of acetyl CoA.
What is the purpose of citrate in the cytoplasm?
Citrate in the cytoplasm also serves as the carbon source for the synthesis of fatty acids and cholesterol; this occurs via the cleavage of citrate into acetyl CoA and oxaloacetate by ATP:citrate lyase.
What is the importance of citrate?
Citrate links many important cellular processes, bridging carbohydrate and fatty acid metabolism and protein modification. Its role in producing acetyl-CoA for the acetylation of histones may turn out to be its most striking role in regulating immune cell function.
How does acetyl-CoA become citrate?
Acetyl-CoA is produced by the breakdown of both carbohydrates (by glycolysis) and lipids (by β-oxidation). It then enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate.
What class of enzyme is citrate synthase?
Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure.
Where is citrate synthase found?
mitochondrial matrix
Citrate synthase is localized within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial. It is synthesized using cytoplasmic ribosomes, then transported into the mitochondrial matrix.
Is citrate synthase a dimer?
However, it functions in the cytsol and is not a dimer but rather a tetramer (9). Algorithmic analysis of citrate synthase based on both primary structure and tertiary structure returned many homologous proteins for comparison.
Where is citrate synthase?
ATP citrate lyase (ACLY) is a cytosolic homotetrameric enzyme that catalyzes the conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate, with the simultaneous hydrolysis of ATP to ADP and phosphate. Interestingly, ACLY is a strategic enzyme linking both the glycolytic and lipidic metabolism.
What are the substrates of ATP citrate synthase?
In enzymology, an ATP citrate synthase (EC 2.3.3.8) is an enzyme that catalyzes the chemical reaction. The 4 substrates of this enzyme are ADP, phosphate, acetyl-CoA, and oxaloacetate, whereas its 3 products are ATP, citrate, and CoA.
What happens when citrate is converted to acetyl-CoA?
By converting citrate to acetyl-CoA, the enzyme links carbohydrate metabolism, which yields citrate as an intermediate, with fatty acid biosynthesis, which consumes acetyl-CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursors of thousands of specialized metabolites, including waxes, sterols, and polyketides.
What does citrate do in the mitochondria?
Since the conversion of pyruvate to acetyl-CoA occurs in mitochondria, and since acetyl-CoA is largely impermeable to mitochondrial membranes, citrate serves as a carrier of carbon atoms between the standard pathway of carbohydrate oxidation, and the pathway of lipid (particularly fatty acid) biosynthesis.