Malate-Aspartate Shuttle

the skeleton muscle cells of our body use a process we call glycerol 3-phosphate shuttle to actually move the NADH molecules produced in the glycolytic pathway from the cytoplasm and into the electron transport chain of the inner membrane of the mitochondria now other cells of our body such as cardiac muscle cells and liver cells use a slightly different shell process and so in this lecture I'd like to focus on a shuttle known as the malate aspartate shuttle and the shuttle is used by cardiac muscle cells and liver cells to actually move the NADH molecules produced in the glycolytic pathway into the matrix of the mitochondria so let's begin by examining the following diagram so in this diagram we have the inner membrane of the mitochondria and we have the matrix side of the mitochondria so this is essentially the cytoplasmic side now in step one we basically want to transform the NADH molecule that is produced in the glycolytic pathway into nad plus and in this process we ultimately extract those two high-energy electrons and we place them onto oxaloacetate in the process we actually reduce oxaloacetate into malate now the reason that we actually want to transform the oxaloacetate into malate is because firstly the oxaloacetate cannot actually move across the mitochondrial membrane and secondly we want to take those electrons from the NADH produced in a glycolytic pathway and transport them onto a molecule that can in fact move across the mitochondrial membrane the outer and the inner mitochondrial membrane so once we actually form the Mallee the Malak now contains the high-energy electrons that were stored on the NADH and the malate can now move across a special anti Porter transport system found on the inner membrane of the mitochondria as the malate moves into the matrix of the mitochondria and alpha keto guru rate is extreme is exchange for that malate and it moves into the intermembrane space and then to the cytoplasm of that particular cell so in step one the NADH that is produced in glycolysis is used to reduce oxalá acetate into malate and what this does is it allows that cell to regenerate the nad Plus that is needed by glycolysis to actually continue glycolysis and it also transfers the pair of electrons from the NADH onto that oxalá acetate to form the malate so that once the malate moves into this side of this matrix of the mitochondria we can actually oxidize that malate back into oxaloacetate and reduce and nad+ found in the matrix into NADH and that NADH can be used by the electron transport chain as we'll see in just a moment so in step two once we form the malate in the cytoplasm of our cell the Mallee then moves into the inter membrane space via the outer membrane of the mitochondria and then that malate enters the matrix of the mitochondria via a special anti Porter transport protein in exchange for an alpha key to gluta rates and in step three in step three we actually take the high-energy electrons on the malate that initially came from NADH and we place him onto that nad plus coenzyme to actually form the NADH so in a way we actually see that the NADH is transported into the matrix of the mitochondria and we also form we reform the oxaloacetate now once the oxaloacetate oh and by the way the enzyme that catalyzes this step the conversion of malate into oxaloacetate is no as the mitochondrial malate dehydrogenase and this is the same enzyme that is used by the citric acid cycle now once we form the oxaloacetate the problem with the oxaloacetate is it can simply pass across the inner membrane of the mitochondria we have to transform the oxaloacetate first into aspartate before it can actually move across this special anti Porter protein system and so the process by which we transform the oxaloacetate into aspartate is known as transamination we essentially take an amino group from another molecule namely the glutamate we place it on to oxaloacetate and that's how we form the aspartate so in step 4 shown here the axial acetate cannot move across the inner mitochondrial membrane and so a transamination reaction converts it into aspartate now in step 5 once we form the aspartate the aspartate can now flow out of the inner membrane of the mitochondria via and exchange a transport system an anti porta system in exchange for glutamate so the aspartate flows out and the glutamate actually flows in now what happens to that glutamate what is glutamate actually used for well glutamate is actually used in the transamination reaction that we mentioned in step 4 that glutamate has an amino group and that amino group is essentially taken or from that glutamate it is placed onto axial or acetate and that's how we form the aspartate and the remaining portion that is left over once we essentially deaminate that glutamate that is what we call alpha ketoglutarate and the alpha ketoglutarate is used to actually help transport the malate in this anti porter Xtreme transport system so in step 6 shown here the glutamate transfers an amino group on to axial acetate and that forms aspartate and the remaining portion of that glutamate is known as alpha keto gluten alpha ketoglutarate now in the final step step seven we have the aspartate that is actually transported back into the cytoplasm of ourselves the aspartate undergoes a reaction to form the oxaloacetate in this process we basically take the aspartate we deaminate that aspartate we remove the amino group and that forms the oxaloacetate and that amino group is actually placed onto the alpha keto glue to rate that enter the cytoplasm via this anti porta system and that transforms the alpha keto glue to rate into glutamate and this essentially completes the cycle in the cycle can repeat itself so in the final step step seven the aspartate in the cytoplasm is deaminated we remove the amino group and we place it onto this alpha ketoglutarate afford that glutamate in the process when we deaminate the aspartate we form that oxaloacetate and now since we reform this molecule the cycle can basically begin all over again so we see that the net result in the malate aspartate shuttle process is we actually move that NADH molecule into the matrix of the mitochondria so we take those high-energy electrons we extract them from the NADH that is produced in glycolysis we place them into a molecule that is then transported into the matrix and then we use those same high-energy electrons to actually form the NADH molecule so in this shuttle process the energy of the NADH is regenerated in the matrix of the mitochondria so we we saw that in the previous discussion when we discuss the glycerol 3-phosphate shuttle we saw that a net result of 1.5 ATP molecules were produced from a single nad age that was gen8 eh that was generated in the process of glycolysis now the question is what is the net quantity of ATP molecules produced by this NADH molecule that is transported into the matrix of the mitochondria via the malate aspartate shuttle process so once the NADH is actually formed within the matrix of the mitochondria it goes on to complex one of the electron transport chain and this is in contrast to the previous shuttle system that we discussed the glycerol phosphate shuttle system in which the NADH actually ends up the electrons on the NADH end up being transferred on to complex 3 so here the NADH is basically we take the NADH that we form in the matrix and we essentially oxidized it into nad plus in this process as the electrons move along the groups within complex one a net result of four ATP molecules are actually transported into the matrix of the into the intermembrane space of the mitochondria now those electrons eventually end up on quinone the quinone becomes the ubiquinone the ubiquinone becomes the ubiquinol and the ubiquinol travels onto complex 3 and those electrons then move on to the groups found within complex 3 and those electrons ultimately end up on cytochrome C and as these electrons move we see that a net result of four of know a 2a H+ ions actually flow flow from the matrix into the intermembrane space and so so far we have four and two that six and as the electrons are transferred from the cytochrome C on too complex for we see that a net result of four ATP of four H+ ions are transferred into the intermembrane space and so a total of four to four so ten h+ ions actually are transferred into the intermembrane space and so now these 10 i 10 ions travel through complex 5 ATP synthase and because 4 protons are needed to pass along the ATP synthase to actually generate a single ATP molecule we see that if we do a little bit of math so we have 10 H+ ions we divide that by 4 H+ ions needed to generate a single ATP molecule that gives us 2.5 ATP molecules are generated every time this NADH is transported into the matrix V and the malate aspartate shuttle system so in the malli aspartate shuttle system the NADH is regenerated in the matrix of the mitochondria therefore in livers so this should be therefore therefore liver and heart cells the NADH produced in glycolysis generates a net result of 2.5 ATP molecules and this is in contrast to the NADH that is produced in glycolysis in cells such as skeletal muscle cells that use the glycerol 3-phosphate shuttle system instead of the malate aspartate shuttle system

Channel: AK LECTURES

Views: 131,022

Rating: 4.9563317 out of 5

Keywords: malate-aspartate shuttle, malate aspartate shuttle, malate shuttle, transport of NADH, transport of NADH into mitochondria, mitochondrial malate dehydrogenase, electron transport chain, mitochondrial transport, biochemistry, pathway of malate-aspartate shuttle, NADH shuttle, NADH transport shuttle, NADH shuttle in heart and liver

Id: nEj8b-sg4ps

Length: 12min 27sec (747 seconds)

Published: Fri Jun 12 2015