In Malate-aspartate shuttle oxaloacetate first convert to malate and then pass inner mitochondrial membrane. in matrix of mitochondria oxaloacetate regenerated from malate.
I think they lack Oxaloactate transporters, so the cells don't have to spend energy to keep oxaloacetate inside the mitochondria.
http://www.life.illinois.edu/crofts/bioph354/lect14&15.html
Basic purpose of malate-aspartate shuttle is to transport reducing power (NADH) generated in cytosol into mitochondria. This shuttle involves two antiporters - one exchanges aspartate with glutamate and the second one exchanges malate with alpha-ketoglutarate. It is obvious that there is no oxaloacetate transporter or oxaloacetate-malate shuttle. To the best of my knowledge oxaloacetate is synthesized and its threshold level is maintained in mitochondria to take care of Kreb's cycle and synthesis of linked organic molecules (in particular keto-acids needed for synthesis of amino acids etc.) .
Dear Dr. Rabbee: Your statement that implies that oxaloacetate does not permeate mitochondrial inner membrane is not correct. The works of Jimpel JA et al.(1973) and Passarella et al., (1977) already showed that oxaloacetate does cross inner mitochondrial membranes in counter-transport with another dicarboxylate or Pi. The real question could be if oxaloacetate is transported at a rate that makes it physiologically relevant. Oxaloacetate would compete with other dicarboxylates for the carriers, and is also metabolized. Besides being an inhibitor of succinate oxidation. Also, what has been found for liver mitochondria does not necessarily apply to other tissue or cell mitochondria. In any case, teleological answers, simple and easily understandable as they are, only lead us to think that mechanisms exist or do not exist because they are good or bad for mitochondrial energetics or the goodness of the Krebs cycle in this case.
Simply because it may not have a membrane transporter (carrier) for this substances.
On the metabolic point of view, the more relevant problem is not if oxaloacetate is transported through the inner mitochondrial membrane but if the malate-aspartate shuttle system is really working in intact cell. Our data obtained with the in vitro reconstituted system and published in “Archives of Biochemistry and Biophysics 518 (2012) 157-163”, indicate that the activity of malate-aspartate shuttle is linked to the amount of α-ketoglutarate generated by glutamate dehydrogenase rather than to the recycling of malate and aspartate between outside and inside the mitochondria as theoretically expected from the functional activity of the shuttle. This comment may give an answer not only to the correct question posed by Dr. Rabbee but also to the arguments given by Dr. Reyes and Dr. Pardha-Saradhi.
The reaction of malate dehydrogenase from malate to oxaloacetate possesses a free Gibbs energy of +29.7 kJ/mole, so the concentration of oxaloacetate is almost one million times lower than malate. A specific transporter would be physiologically not used because of the very low concentration of the oxaloacetate. Recall that the next reaction on the Krebs cycle is very spontaneous, with Gibbs free energy of -31.5 kJ/mole, which allows keeping the efficiency of the Krebs cycle.
Yes, malate dehydrogenase is producing oxaloacetate only if the concentration of the last compound is maintained at low level! That is also why malate dehydrogenase is quite often measured in the direction of malate production. The activity of this enzyme could be measured in the direction of oxaloacetate formation if in the assay oxaloacetate is "removed" for ex. by coupling with citrate synthase (oxaloacetate + Acetyl-CoA).
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