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malate-aspartate shuttle

General Background The rates of oxidation and reduction of : NAD and : NADH must be continuously balanced within the cell to maintain the pathways of anabolism and catabolism. : NADH produced in the cytosol during : PWY66-400 needs to be oxidized to : NAD and the NADH oxidation process in the cell occurs primarily via mitochondrial respiration. NADH is the reducing equivalent that supplies electrons to the electron transport chain to generate ATP. NADH cannot traverse the inner mitochondrial membrane and cytosolic reducing equivalents (hydrogen atoms) must be transferred to the mitochondria across the membrane via metabolite shuttles that operate between the two compartments . The : MALATE-ASPARTATE-SHUTTLE-PWY is a biochemical entity that facilitates the translocation of electrons across the membrane. The shuttle involves a reaction between NADH and an oxidized substrate in the cytosol, the reduced substrate is transported into the mitochondrion and subsequently reoxidized by the electron transfer chain. There are two well established shuttles for the transport of reducing equivalents described for vertebrates, the : MALATE-ASPARTATE-SHUTTLE-PWY and the : PWY-6118. About this Pathway The shuttle consists of six key component proteins, : CPLX-7322, : CPLX66-376, : CPLX66-371, : CPLX66-370, : ENSG00000115840-MONOMER and : ENSG00000108528-MONOMER. : CPLX-7322 "Cytosolic malate dehydrogenase" catalyzes the transfer of two electrons from : NADH and a proton from : OXALACETIC_ACID to form : MAL . Subsequently, : ENSG00000108528-MONOMER simultaneously imports malate into the mitochondrial matrix from the cytosol and exports : 2-KETOGLUTARATE from the matrix to the cytosol. Malate is then converted back to oxaloacetate by : CPLX66-376, NAD+ is reduced to NADH and a proton is released . Oxaloacetate cannot cross the mitochondrial membrane. It acquires an amino group from : GLT in a transamination reaction catalyzed by : CPLX66-370, and is transformed to : L-ASPARTATE . This also produces : 2-KETOGLUTARATE and both : L-ASPARTATE and : 2-KETOGLUTARATE are transported across the inner mitochondrial membrane. The transporter : ENSG00000115840-MONOMER simultaneously transports glutamate from the cytosol to the mitochondrial matrix while exporting aspartate from the matrix to the cytosol . In the cytosol, oxaloacetate is regenerated by reversal of the same transamination reaction catalyzed here by : CPLX66-371. This shuttle is reversible, so electrons from NADH are brought into the mitochondrion when the NADH/NAD+ ratio is higher in the cytosol than in the mitochondrial matrix. The malate-aspartate shuttle yields approximately 3 molecules of ATP per molecule of cytosolic NADH and is found in liver, heart and kidney . It is quantatively the most important shuttle for the reoxidation of cytosolic NADH in vertebrate tissues under aerobic conditions. This pathway also describes aspartate biosynthesis and degradation.

Type: pathway
Taxonomic scope
organism-specific biosystem
Homo sapiens

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