This entry represents the adenylate kinase 2 (AK2) subfamily of the adenylate kinases (AKs), which are nucleoside monophosphate kinases that catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors. Proteins in this entry include AK2 from humans, Adk1 from budding yeasts. In humans, nine different AK isoenzymes have been identified (AK1-9). AK2 is the major mitochondrial isoform and is expressed in the mitochondrial intermembrane space of tissues rich in mitochondria such as liver, heart and skeletal muscle []. Mutations in AK2 gene cause the reticular dysgenesis (aleukocytosis), which is the most severe form of inborn severe combined immunodeficiencies []. In budding yeasts, Adk1 (also known as Aky2) is the major isoform of AKs. It is found in both cytoplasm and mitochondrial intermembrane space. It has no cleavable mitochondrial targeting sequence [].
Aspartate kinase () (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine [].In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.This entry represents a region encoding aspartate kinase activity found in both the monofunctional and bifunctional enzymes.Synonym(s): Aspartokinase
Adenylate kinases (ADK) are phosphotransferases that catalyse the reversible reaction AMP + MgATP = ADP + MgADPan essential reaction for many processes in living cells. Two ADK isozymes have been identified in mammalian cells. These specifically bind AMP and favour binding to ATP over other nucleotide triphosphates (AK1 is cytosolic and AK2 is located in the mitochondria). A third ADK has been identified in bovine heart and human cells [], this is a mitochondrial GTP:AMP phosphotransferase, also specific for the phosphorylation of AMP, but can only use GTP or ITP as asubstrate []. ADK has also been identified in different bacterial species and in yeast []. Two further enzymes are known to be related to the ADK family, i.e. yeast uridine monophosphokinase and slime mold UMP-CMP kinase. Within the ADK family there are several conserved regions, including the ATP-binding domains. One of the most conserved areas includes an Arg residue, whose modification inactivates the enzyme, together with an Asp that resides in the catalytic cleft of the enzyme and participates in a salt bridge.In humans, nine different AK isoenzymes have been identified (AK1-9) [].
Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see [].Aspartate kinase () (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine [].In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.
