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Oxaloacetate is an intermediate of the citric acid cycle, where it reacts with acetyl-CoA to form citrate, catalyzed by citrate synthase. It is also involved in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, and fatty acid synthesis. Oxaloacetate is also a potent inhibitor of complex II.
Citrate synthase (E.C. 2.3.3.1 (previously 4.1.3.7)) is an enzyme that exists in nearly all living cells. It functions as a pace-making enzyme in the first step of the citric acid cycle (or Krebs cycle ). [ 5 ]
However, in the presence of high levels of malate and NAD +, citrate can stimulate the production of oxaloacetate. Although malate dehydrogenase is typically considered a reversible enzyme, it is believed that there is an allosteric regulatory site on the enzyme where citrate can bind to and drive the reaction equilibrium in either direction. [19]
The reaction it catalyzes is: pyruvate + HCO − 3 + ATP → oxaloacetate + ADP + P. It is an important anaplerotic reaction that creates oxaloacetate from pyruvate. PC contains a biotin prosthetic group [1] and is typically localized to the mitochondria in eukaryotes with exceptions to some fungal species such as Aspergillus nidulans which have a cytosolic PC.
Beta oxidation, in the mitochondrial matrix, then cuts the long carbon chains of the fatty acids (in the form of acyl-CoA molecules) into a series of two-carbon units, which, combined with co-enzyme A, form molecules of acetyl CoA, which condense with oxaloacetate to form citrate at the "beginning" of the citric acid cycle. [2]
Citrate also inhibits malate oxidation, but only at low malate or NAD concentrations. When both malate and NAD concentrations are high (10 mmol/L and 5 mmol/L, respectively), citrate can actually augment MDH2 activity. [10] All three effectors (malate, oxaloacetate and citrate) bind to the same putative allosteric site. [11]
Citrate ion Malate ion. The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. [1] Mitochondria are enclosed in a double membrane.
oxaloacetate + acetyl-CoA + H 2 O → citrate + CoASH; catalyzing enzyme: citrate synthase, EC 2.3.3.1 Reaction steps from malate to pyruvate and lactate.