Transcript for:
Understanding the Malate-Aspartate Shuttle

hey everyone in this lesson we are going to talk about mad ASP parted shuttle so to start with the background I first want to talk about the cellular respiration and when it comes to glycolysis cellular respiration is broken down into four different stages in glycolysis which takes place in the cytool one molecule of glucose is broken down into two molecules of pyu and during the process it also generates twoh in the cytool now second stage is the oxidation of pyoid so oxidative decarbox silation of pyate converts pyate into acti coenzyme a and this reaction takes place in the mitochondrial metrix and during the reaction it also generates 2 nadh these are supposed to be 2 nadh because the initial reaction involves two molecules of pyate now third stage is the oxidation of acety coenzyme and this reaction is carried out through TCA cycle or citric acid cycle or crep cycle and during the reaction acetel coenzyme is oxidized into carbon dioxide and the electrons which are liberated through these oxidative processes are passed on to coenzymes such as NAD and fad which are then reduced to nadh and fadh2 and this reaction also takes place in the mitochondrial Matrix and last stage is the electron transport chain and oxidative phosphorilation and during this reaction fa NAD and fadh2 as well as n DH from oxidated carox of pyate reaction give up their electrons to electron transport chain to synthesize ATP now one important thing to remember that nadh used in the electron transport chain is generated in the mitochondrial Matrix however nadh is also generated in the cytool through glycolysis process but the biggest problem is nadh just simply cannot cross the mitochondrial Matrix to be oxidized to synthesize ATP so the question is what happens to the cytosolic nadh and how is it oxidized to synthesize ATP in the mitochondria so during glycolysis when glycer alide 3 phosphate is converted into 13 B phosphoglycerate with the help of enzyme glycer alide three phosphate dehydrogenase during the reaction nad+ is reduced to nadh and remember that if this nadh is not oxidized to regenerate nad+ the glycolytic pathway would cease to function due to the unavailability of nad+ so one very important reason for nadh to oxidize is to regenerate nad+ in order for glycolysis to continue and to regenerate nad+ nadh must be oxidized and there are basically two different ways how nadh could be oxidized now one is during anerobic pathway so during anerobic condition pyate is converted into lactate with with the help of lected dehydrogenase enzyme and during the reaction nadh is oxidized into nad+ and this NAD plus is then useful in the glycolysis reaction now in Aerobic condition nadh must be oxidized into nad+ via respiratory chain or electron transport chain however as I mentioned NADA just simply cannot pass the mitochondrial membrane to be oxidized into nad+ so one way to resolve this issue is electrons from nadh are carried across cross mitochondrial membrane but not nadh itself so basically what I mean by is suppose here we have nadh in the cytool and it is carrying these electrons so nadh is oxidized into nad+ and electron from this nadh are then carried across the mitochondrial membrane and in the mitochondria these electrons are then passed on to nad+ and nad+ is then reduced to nadh so basically we are regener generating this nadh into mitochondria and once this nadh is regenerated it is then going to give up its electron to electron transport chain to synthesize ATP so now the question is how is this cytoplasmic nadh oxidized into mitochondria to synthesize ATP so basically there is a shuttle system which helps carrying these electrons from cytoplasmic and ADH into the mitochondria and there are two different types of shuttle and one of these shuttles is called Mallet as CED shuttle and through this shuttle electrons from nadh in the cytool they are carried across the mitochondrial membrane through Mallet aspartate shuttle and in the mitochondria these electrons are passed on to nad+ which is then reduced to NAD and this nadh is then gives up it its electron to respiratory chain to synthesize ATP as we have learned before that one nadh synthesizes 2.5 molecules of ATP so basically through Mallet as parted shuttle one cytosolic nadh synthesizes 2.5 molecules of ATP in the mitochondria now this shuttle operates heavily in the heart liver and kidneys now let's talk about how this shuttle works so here we have nadh from glycolysis that is in the cytool so this is basically a cytosolic nadh and this is the cytool and this is the mitochondrial Matrix part and this is the inner mitochondrial membrane so the first step in this malet aspartate shuttle is it requires oxaloacetate and oxaloacetate basically acquires electrons from cytosolic nadh and gets reduced into malet and the reaction is catalyzed by malet De hydrogenous enzyme which is actually the cytosolic enzyme and once oxaloacetate is reduced to malet this Mallet from the cytool is then transported across mitochondrial membrane to enter into mitochondrial Matrix and during the reaction while oxaloacetate is acquiring electrons from nadh nadh is oxidized to nad+ and this nad+ is then enter into glycolysis pathway and ensures that glycolysis pathway is continued to function so basically the electrons are carried in the form of Mallet from cytool to mitochondrial Matrix now once inside the mitochondrial Matrix through reverse reaction Mallet is then converted back into oxal acid with the help of mitochondrial malet dehydrogenase enzyme and during the reaction electrons from malet is then passed on to nad+ and which is then reduced to nadh so here we have regenerated nadh and this nadh then enters into electron transport chain to synthesize ATP now this oxaloacetate in the mitochondria cannot cross the mitochondrial membrane therefore oxaloacetate must be transaminated to convert it into aspartate and the reaction is catalyzed by aspartate aminot transferase now once oxaloacetate is transaminated into aspartate this aspartate is now able to cross the mitochondrial membrane to enter into cytool now the question is where does this amino group of aspartate come from and it is important to know that this amino group of aspartate is being donated by glutamate so when glutamate is deaminated basically when it donates is amino group to aspartate glutamate is converted into alpha alpha ketoglutarate and what happens to Alpha ketoglutarate we are going to talk about this shortly I first want to quickly talk about what happens to aspartate once it is in the cytool so once inside the cytool aspartate is then transaminated to synthesize oxaloacetate so basically we are able to now regenerate oxaloacetate in the cytool and the reaction is catalyzed by Esparto aminase enzyme which is present in the cytool so once Alpha ketoglutarate is synthesized in the mitochondria it is then transported from mitochondria into cytool in exchange for malet through malet Alpha ketoglutarate transporter basically this is an antiporter so what antiporter means is it is actually a protein which allows the transport of two molecules at the same time but in different directions so malet is transfered from cytool to mitochondria whereas Alpha ketoglutarate is transported from mitochondria into cytool now once Alpha ketoglutarate is in the cytool is then transaminated to form glutamate with the help of aspartate amino transferase and glutamate from cytool is then transported in the mitochondria in exchange for aspartate through aspartate glutamate transporter and this is another antier which transports glutamate and aspartate at the same time in different direction so this is basically the overview of Mallet as parted shuttle so let me just quickly go through it again basically oxal acid in the cytool acquires electron from nadh and reduced into malate with the help of malet dehydrogenase enzyme and during the reaction nadh is oxidized to NAD plus and NAD plus then enters into glycolysis now malage which is synthesized in the cytosol is then entered into mitochondria and through reverse reaction Mallet is then converted back into o solo acetate with the help of mitochondrial malet dehydrogenase enzyme and in the reaction malet is then pass the electrons to NAD plus and NAD plus is then reduced to nadh which is then enter into which then enters into electron transport chain to synthesize ATP now oxaloacetate in the mitochondria cannot cross the mitochondrial me membrane therefore it must be transaminated to form aspartate with the help of aspartate aminot transferase enzyme and the amino group on aspartate is is donated by glutamate and during this deamination of glutamate glutamate is converted into Alpha ketoglutarate now aspartate from the mitochondria is then be then able to cross the mitochondrial membrane to enter into cytool now in the cytool aspartate is then transaminated to oxal aate with the help of cytosolic aspartate aminot transference enzyme now Alpha ketoglutarate in the mitochondria is then transported into cytool in exchange for malet with the help of malet alpha kogut transporter and in the cytool Alpha kog glutide is then transaminated to form glutamate now glutamate from cytool enters into mitochondria in exchange for aspartate through aspartate glutamate transporter so this is basically the overview of malet aspartate shuttle now I also want to quickly talk about that once nadh is regenerated in the mitochondria through malet sped shuttle this nadh then gives up its electron to complex one and the electrons from complex one then travels from complex one one to coenzyme Q to complex 3 to cytochrom C to complex 4 and finally to the final electron acceptor that is oxygen and during this process protons are being pumped out from the mitochondrial Matrix into the Inner intermembrane Space and these protons are then passed through the complex 5 which is the ATP synthes enzyme and when the electrons pass through the ADP synthes enzyme ADP is phosphorilated to synthesize ATP and one nadh is able to synthesize 2.5 molecules of ATP so this is basically the overview of malet ASP parted shuttle where cytosolic nadh is oxidized into mitochondria to synthesize ATP I really hope you learn something new from this video and if you do so then please like share and subscribe the channel thank you so much for watching and I'll see you again soon