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.
Gluconeogenesis Gluconeogenesis is a metabolic pathway consisting of a series of eleven enzyme-catalyzed reactions, resulting in the generation of
glucose from non-carbohydrate substrates. The beginning of this process takes place in the
mitochondrial matrix, where
pyruvate molecules are found. A pyruvate molecule is carboxylated by a
pyruvate carboxylase enzyme, activated by a molecule each of
ATP and water. This reaction results in the formation of oxaloacetate.
NADH reduces oxaloacetate to
malate. This transformation is needed to transport the molecule out of the
mitochondria. Once in the
cytosol, malate is oxidized to oxaloacetate again using NAD+. Then oxaloacetate remains in the cytosol, where the rest of reactions will take place. Oxaloacetate is later
decarboxylated and
phosphorylated by
phosphoenolpyruvate carboxykinase and becomes
2-phosphoenolpyruvate using
guanosine triphosphate (GTP) as phosphate source. Glucose is obtained after further downstream processing.
Urea cycle The
urea cycle is a metabolic pathway that results in the formation of
urea using one ammonium molecule from degraded amino acids, another ammonium group from aspartate and one bicarbonate molecule. It is an
anabolic pathway occurring in
plants and
bacteria utilizing the enzymes
isocitrate lyase and
malate synthase. Some intermediate steps of the cycle are slightly different from the citric acid cycle; nevertheless oxaloacetate has the same function in both processes. Part of this reducing power is generated when the cytosolic oxaloacetate is returned to the mitochondria as long as the internal mitochondrial layer is non-permeable for oxaloacetate. Firstly the oxaloacetate is reduced to malate using NADH. Then the malate is decarboxylated to pyruvate. Now this pyruvate can easily enter the mitochondria, where it is carboxylated again to oxaloacetate by pyruvate carboxylase. In this way, the transfer of acetyl-CoA that is from the mitochondria into the cytoplasm produces a molecule of NADH. The overall reaction, which is spontaneous, may be summarized as: :HCO3– + ATP + acetyl-CoA → ADP + Pi + malonyl-CoA
Amino acid synthesis Six essential amino acids and three nonessential are synthesized from
oxaloacetate and pyruvate. Aspartate and alanine are formed from oxaloacetate and pyruvate, respectively, by transamination from
glutamate. Asparagine is synthesized by amidation of aspartate, with glutamine donating the NH4. These are nonessential amino acids, and their simple biosynthetic pathways occur in all organisms. Methionine, threonine, lysine, isoleucine, valine, and leucine are essential amino acids in humans and most vertebrates. Their biosynthetic pathways in bacteria are complex and interconnected.
Oxalate biosynthesis Oxaloacetate produces oxalate by hydrolysis. :oxaloacetate + H2O oxalate + acetate This process is catalyzed by the
enzyme oxaloacetase. This enzyme is seen in plants, but is not known in the animal kingdom. == Interactive pathway map ==