![]() ![]() The mitochondrial carrier aspartate-glutamate carrier (AGC) and the aspartate transporter ODC1-2 are essential for malate-aspartate shuttle function. ![]() ![]() ![]() The malate-aspartate shuttle consists of two different enzymes, one in the matrix and one in the intermembrane space. Nicotinamide adenine dinucleotide (NADH) is impermeable to the inner membrane of mitochondria and so aspartate is a key component for carrying reducing equivalents across the membrane. The malate-aspartate shuttle is a biochemical system that transports electrons from glycolysis into the electron transport chain of the mitochondria. During this process, a network of transporters allows for the net import or export of a variety of citric acid cycle intermediates. Another transporter exchanges aspartate for malate, which allows it to shuttle between reducing and nonreducing equivalents. The transporter transports succinate on the dicarboxylate carrier, which exchanges malate with citrate on the tricarboxylate carrier. The transport fluxes of the malate-aspartate shuttle involve proton exchange between the two species. The concentration of the two metabolites determines the direction of transport. One of the transporters, malate dehydrogenase, removes aspartate from the intermembrane space and facilitates the transfer of glutamate into the mitochondria. In mitochondria, the malate-aspartate shuttle involves two transporters that facilitate the transfer of equal molar equivalents of the two metabolites in opposite directions. Although the shuttle has a complex biochemistry, there are several common roles that it plays. The mitochondria uses these electrons for oxidative phosphorylation. (This definition may be outdated - see the DesignNote.The malate-aspartate (MA) shuttle is a biochemical system that transports the electrons produced during glycolysis across the mitochondrion’s semipermeable inner membrane. The overall result is that NADH is transported into the mitochondria, and can be used to generate 3 ATP per every NADH transported in from the cytosol, a very efficient process. Aspartate is returned to the cytosol by the aspartate-glutamate transporter, which moves glutamate into the mitochondria as it transports aspartate out. The oxaloacetate is transaminated with glutamate to make aspartate and alpha-ketoglutarate. Malate aspartate shuttle free#This NADH is then free to transfer its high energy electrons to the electron transport chain. Once inside, the energy in malate is extracted again by reducing NAD+ to make NADH, regenerating oxaloacetate. Malate and the electrons it carries are transported into the mitochondria across the inner mitochondrial membrane, in exchange for alpha-ketoglutarate, which is transported out of the mitochondria. First, oxaloacetate on the cytoplasmic side is reduced by NADH, creating malate and NAD+. The malate-aspartate shuttle occurs in mammalian tissues. One shuttle is the glycerophosphate shuttle and another is the malate-aspartate shuttle. Instead shuttle mechanisms have evolved to move the energy of reduced NADH across the membrane in the form of other reduced molecules. NADH generated during glycolysis cannot reach the electron transport chain directly however and there is no direct mechanism for the transfer of NADH across the mitochondrial membrane. This NADH comes primarily from the Krebs cycle in the mitochondrial matrix and is therefore directly accessible to electron transport. Most of the energy derived from the oxidation of glucose is not extracted directly as ATP, but as reduced NADH that transfers high-energy electrons to the electron transport chain in the inner mitochondrial membrane. ![]()
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