Malate-aspartate shuttle

The malate aspartate shuttle ( malate cycle), is a system for indirect transfer of the reducing agent NADH, from the cytosol into the mitochondrial matrix.

Operation

The shuttle system consists of four different enzymes and two antiport carriers.

The working cycle begins with the NADH-dependent reduction of the oxaloacetate to malate. As this enzyme cytosolic malate dehydrogenase ( CMDh ) is active, an isoenzyme of the mitochondrial malate dehydrogenase involved in the citric acid cycle ( mMDH ). The malate formed is transported through the α -ketoglutarate -malate into the carrier matrix of the mitochondria, wherein α -ketoglutarate in antiport passes into the cytosol. α - Ketoglutarate is used at a later stage of the cycle to regenerate the cytosolic oxaloacetate.

Inside the mitochondrion mitochondrial malate dehydrogenase oxidizes the imported malate back to oxaloacetate, where NAD to NADH H is reduced. The actual transport function of the Shuttle is thus already fulfilled, but further steps are necessary to maintain the cycle. Thus, the oxaloacetate is aminated to aspartate glutamate - dependent in the mitochondrion via a mitochondrial aspartate aminotransferase ( MAST). Here, α -ketoglutarate formed from glutamate. Glutamate originates from the cytosol, where it is exchanged with the aspartate glutamate carrier against the resulting aspartate.

In the last step of the cycle, the aspartate in the cytosol by a cytosolic aspartate aminotransferase ( CAST) to oxaloacetate, the starting material for the first reaction, implemented. In this case, the transported in exchange for malate into the cytosol α -ketoglutarate is converted to glutamate. This can be conveyed by the said aspartate - glutamate carrier back into the matrix space.

Biological Significance

The shuttle system is necessary so that the NADH produced in glycolysis and a localized in the mitochondrial respiratory chain, can be supplied in order there to serve as an energy carrier for the synthesis of ATP. NAD is regenerated at the same time so that it can be used again in the glycolysis. It occurs in mammals, both in the mitochondria of the heart, the liver and the kidneys. In the transport process, it is not an active transport, so it can not NADH gradients are on, but only reduced. So that a preponderance of the cytosolic NADH concentration as compared to mitochondrial required for a directional transport into the mitochondrion.

In other tissues, particularly in muscle, or in the brain cytosolic NADH is fed by a more rapid transport system of the respiration chain, by the so-called glycerol -3-phosphate shuttle.

The by the shuttle system transported into the cytosol oxaloacetate can be also used for gluconeogenesis.

Classification in the metabolic context

The malate - aspartate shuttle is - in addition to the glycerol-3 -phosphate shuttle - one of the main ways of transporting electrons / reducing equivalents from the cytosol into the mitochondria dar. Unlike glycerol-3 -phosphate shuttle system is energy efficient because the in the matrix generated NADH can be fed directly into the respiratory complex I. The glycerol-3- phosphate shuttle system, however, the energy weaker flavin adenine dinucleotide FADH 2, the electrons can pass through only in the ubiquinone respiratory complex III is formed. Thus providing a cytosolic NADH using the malate -aspartate shuttle in the respiratory chain about 2.5 ATP, whereas it produced only approximately 1.5 ATP during transport by the glycerol -3-phosphate shuttle.