1. Malate-Aspartate Shuttle
Malate-a-Ketoglutarate Transporter
NAD+
NAD+
MDH2
MDH1
NADH
NADH
Review:
The Malate (L-Malic Acid)-Asp (Aspartate or L-Aspartate or Aspartic Acid) Shuttle of mammalian systems is more complex but more energy efficient. Mitochondrial NAD+ (Nicotinamide Adenine Dinucleotide) is reduced by cytosolic NADH (Nicotinamide Adenine Dinucleotide, Reduced) through the intermediate reduction and subsequent regeneration of OAA (Oxaloacetate) (Ref.1). In the cytosol, the shuttle converts OAA to Malate using the enzyme MDH1 (Malate Dehydrogenase-Cytoplasmic), and at the same time re-oxidizes NADH to NAD+, making it available for Glucose oxidation. Malate is then shuttled into the mitochondria by a Malate-Alpha-Ketoglutarate Transporter. In the mitochondria, the reverse reaction takes place and Malate is again converted to OAA by the enzyme MDH2 (Malate Dehydrogenase-Mitochondrial) (Ref.2). The shuttle is completed with a second enzyme, GOT2 (Glutamate Oxaloacetate Transaminase-Mitochondral)/Aspartate Aminotransferase (Mitochondrial), which produces Asp from OAA in the mitochondral matrix. Aspartate is then transported into the cytosol by the Glutamate-Aspartate Transporter in exchange for cytosolic Glutamate (Glutamic Acid), where it is re-converted into OAA by GOT1 (Glutamate Oxaloacetate Transaminase-Soluble)/Aspartate Aminotransferase (Cytosolic) in conjuction with Alpha-Ketoglutarate conversion to Glutamate. The ratio of NADH/NAD+ is increased in the matrix and decreased in the cytosol by this system, even though no NADH has crossed the inner membrane. The overall result is that NADH is transported into the mitochondria and is used to generate 3 ATP (Adenosine Triphosphate) per every NADH transported in from the cytosol, a very efficient process (Ref.3).
References:
1. Arai T, Inoue A, Uematsu Y, Sako T, Kimura N.
Activities of enzymes in the malate-aspartate shuttle and the isoenzyme pattern of lactate dehydrogenase in plasma and peripheral leukocytes of lactating Holstein cows and riding horses.
Res. Vet. Sci Aug;75(1):15-9.
PubMed ID:
2. Barron JT, Gu L, Parrillo JE.
Malate-aspartate shuttle, cytoplasmic NADH redox potential, and energetics in vascular smooth muscle.
J. Mol. Cell Cardiol Aug;30(8):
PubMed ID:
3. Indiveri C, Kramer R, Palmieri F.
Reconstitution of the malate/aspartate shuttle from mitochondria.
J. Biol. Chem Nov 25;262(33):
PubMed ID:
Inner Mitochondrial Membrane
GOT2
GOT1
Glutamate-Aspartate Transporter
Mitochondrial Matrix
Cytosol