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Since aspartate is an amino acid, an amino radical needs to be added to the oxaloacetate. This is supplied by glutamate, which in the process is transformed into alpha-ketoglutarate by the same enzyme. The second antiporter (AGC1 or AGC2) imports glutamate from the cytosol into the matrix and exports aspartate from the matrix to the cytosol.
The two main systems in humans are the glycerol phosphate shuttle and the malate-aspartate shuttle. The malate/a-ketoglutarate antiporter functions move electrons while the aspartate/glutamate antiporter moves amino groups. This allows the mitochondria to receive the substrates that it needs for its functionality in an efficient manner. [1]
EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1). EAAT1 is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space. [6] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle. [7]
glutamate oxaloacetate transaminase (GOT), also called aspartate transaminase (AST), EC 2.6.1.1 (component of the malate aspartate shuttle) Recruited reaction steps of the citric acid cycle and malate aspartate shuttle
GOT2 and another enzyme, MDH, are essential for the functioning of the shuttle. GOT2 converts oxaloacetate into aspartate by transamination. This aspartate as well as alpha-ketoglutarate return into the cytosol, which is then converted back to oxaloacetate and glutamate, respectively. [8]
As a member of the malate-aspartate NADH shuttle, Aralar is also involved in the transfer of cytosolic reducing equivalents from the cytosol to the mitochondrial matrix. [17] Aralar, along with the protein encoded by SLC25A13, are both calcium-binding aspartate/glutamate carriers which are substrates in the TIMM8A/TIMM13 complex.
These reactions are facilitated by transaminases in order to produce aspartate and asparagine from oxaloacetate. Transamination of α-ketoglutarate produces glutamate, proline, and arginine. These amino acids are then used either within the matrix or transported into the cytosol to produce proteins. [7] [13]
Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate. The EAATs are membrane-bound secondary transporters that superficially resemble ion channels. [1]