Glycerol 3-Phosphate Shuttle

the process of glycolysis allows cells to actually generate ATP molecules in the process and also generates nadh molecules now for glycolysis to actually continue taking place the nad plus molecules that are used up in glycolysis must be regenerated and that's because nad plus concentration is limited inside our cells and under aerobic conditions when we have oxygen present side ourselves these nad plus molecules are regenerated on the electron transport chain so the nad plus the NADH molecules that we form in glycolysis must somehow move on to the electron transport chain found on the inner membrane of the mitochondria and there the electrons are extracted from the NADH to form the energy plus and electrons are also used to actually generate ATP molecules so the question that I'd like to focus on in this lecture is how exactly do the NADH molecules produced in the process of glycolysis actually get to the electron transport chain so once again under aerobic conditions NADH molecules produced in glycolysis must be transported into the mitochondria why well because the cell must use the NADH molecules to not only produce ATP molecules but to also regenerate the nad plus coenzyme that is needed for glycolysis to actually continue taking place now they're actually different ways by which the NADH molecules can actually get into the mitochondria and in this lecture I'd like to focus on a specific type of membrane transport system known as the glycerol 3-phosphate shuttle and this is the shuttle that is used predominantly by skeletal muscle cells of our body so the inner mitochondrial membrane is actually impermeable to nad plus or NADH molecules and that means these NADH molecules once form in glycolysis not simply move across the membranes of the mitochondria and their movement basically depends on a specialized membrane transport system that we call glycerol 3-phosphate shuttle so let's begin in glycolysis so in glycolysis we oxidize glucose into pyruvate molecules in the process we also generate these NADH molecules now once the NADH molecule is formed in the process of glycolysis it remains in the cytoplasm and what happens to it is a special enzyme known as cytoplasmic glycerol 3-phosphate dehydrogenase actually oxidizes the NADH back into nad plus that regenerates the nad plus coenzyme needed for glycolysis and what this process also does is it passes those high-energy electrons from the NADH unto a molecule known as DHAP dihydroxyacetone phosphate and this is the same molecule that we find as an intermediate in the glycolytic pathway so in process one NADH plus a proton reacts with the DHAP and intermediate of glycolysis so we essentially reduce this molecule into g3p where g3p stands for glycerol 3-phosphate and that's why this is known as the glycerol 3-phosphate shuttle because once we form the g3p the g3p can now move across the outer membrane of the mitochondrion enter the intermembrane space so in step one in the cytoplasm NADH produced in glycolysis is oxidized back into nad plus by reducing dihydroxyacetone phosphate DHAP into glycerol 3-phosphate g3p and this reaction allows us to regenerate the energy plus needed for the glycolytic pathway and also allows us to actually pass electrons unto a molecule that can now move into the intermembrane space of the mitochondria and this is catalyzed by the cytoplasmic glycerol 3-phosphate dehydrogenase enzyme now once that g3p actually moves into the intermembrane space of the mitochondria it is now oxidized back into DHAP by an enzyme that is found on the outer portion of the inner membrane of the mitochondria and this enzyme shown here in orange is actually an isis i'm version of this cytoplasmic glycerol 3-phosphate dehydrogenase enzyme and so we call this enzyme the mitochondrial version glycerol 3-phosphate dehydrogenase or simply the mitochondrial glycerol 3-phosphate dehydrogenase now what this enzyme actually does is it oxidizes the g3 P into G H AP by taking off those two electrons and two protons and placing them onto an F ad molecule that is bound to that enzyme so F ad is flavin adenine dinucleotide and it can accept two protons and two electrons so in step number two we see that the enzyme transfers the two electrons and two protons from the g3p onto fa d to form the fadh2 and in a final step of the glycerol 3-phosphate shuttle the fadh2 is actually oxidized back into fa d in the process those two electrons and the two protons that ultimately came from these two reactants here are basically transferred onto ubiquinone that is found within a hydrophobic core of the inner membrane of the mitochondria and we reduce that ubiquinone into ubiquinol now remember back in our discussion on electron transport chain we said that ubiquinone calories high-energy electrons and the protons on two complex three of the electron transport chain so if this is our electron transport chain we have complex 1 complex 2 complex 3 4 and complex 5 this molecule here is this mitochondrial glycerol 3-phosphate dehydrogenase that we discussed in this diagram and so ultimately the two electrons are passed onto this molecule and then the ubiquinone takes those two electrons and becomes ubiquinol and passes those two electrons directly on to complex 3 and what that means is we essentially bypass complex one because when the NADH molecules are produced in the citric acid cycle because the citric acid cycle takes place in the matrix of the mitochondria these NADH molecules actually pass down their electrons on to complex one of the electron transport chain but the NADH molecules produced in the cytoplasm via glycolysis they actually pass down their electrons on to complex 3 via this enzyme known as glycerol 3-phosphate dehydrogenase so because of that what actually happens is that net number of ATP molecules produced by the NADH which is formed glycolysis is only 1.5 compared to a value of 2.5 that is produced by NADH molecules form in the citric acid cycle and to see what we mean let's take a look at the following calculation so let's get a red marker and a black marker okay so for those NADH molecules produced in the matrix of the mitochondria via the citric acid cycle these NADH molecules are oxidized back into nad plus a long complex one of the electron transport chain and when these two electrons travel through and ultimately end up on ubiquinone a net result of four protons are pumped into the intermembrane space of the mitochondria so when these electrons travel through complex one this pumps four protons now these two electrons are collected by ubiquinone that becomes ubiquinol ubiquinol then travels through the core of the membrane and attaches onto complex three and complex 3 then moves those electrons ultimately on to cytochrome C in the process a total of 2 a net result of 2 protons are actually pumped across the membrane from the matrix and into the intermembrane space and finally cytochrome C carries those electrons onto complex 4 and in complex 4 as those electrons are travel through the complex and ultimately are used to reduce oxygen into water we pump a net result of 4 ATP molecules from the matrix of the mitochondria into the intermembrane space and so when a single nadh molecule produced in the citric acid cycle found in the matrix is oxidized into nad plus by the electron transport chain we transport a net result of for 2 & 2 so 10 protons into the intermembrane space now these 10 protons then move via complex 5 also known as ATP synthase to actually generate those ATP molecules and recall from the previous discussion 4 protons are needed to actually generate a single ATP molecule and so we see that we have a total of 10 H+ ions pumped into the intermembrane space by this NADH produced in a citric acid cycle we need 4 H+ ions to generate a single ATP molecule and so we divide these numbers we get a value of 2.5 of ATP molecules are generated when a single NADH produced by the citric acid cycle is oxidized into nad plus by the electron transport chain now let's carry out the same calculation except now we do it for the NADH produced by glycolytic pathway which takes place in a cytoplasm because NADH actually passes down electrons to the DHAP to form the g3p and then the g3p goes into the inner membrane of the mitochondria binds up to this enzyme here and so ultimately those two electrons on the NADH produced in the glycolytic pathway actually end up on this protein and then they're picked up by ubiquinone to form ubiquinol and so NADH bypasses complex one and that means as the electrons pass down to ubiquinol that ubiquinol travels and attaches onto complex 3 and so now two protons are pumped here four protons are pumped here so we form a net result of six protons in this case as compared to the 10 protons in the previous case and so now six H+ ions divided by we still need four H+ to generate a single ATP we form 1.5 ATP per single NADH that is oxidized that is produced in the glycolytic pathway so from this conclusion from this result we can conclude the following since the mitochondrial membrane is impermeable to NADH the solution to actually transporting the NADH is not actually moving the NADH but rather transporting those electrons onto a different molecule then moving that molecule across the outer membrane and using that molecule to move the electrons onto this enzyme which then moves those electrons on to ubiquinone so since the mitochondrial membrane is a permeable to nadh molecules the solution is to extract electrons from nadh produced in the glycolytic pathway and ultimately pass them down to ubiquinone to form ubiquinone and then ubiquinone ubiquinol essentially completely bypasses complex one because it gives the two electrons on two complex three and since nadh from glycolysis bypasses complex one it only produces a net result of 1.5 ATP molecules rather than the 2.5 which are produced from the NADH that is formed in the citric acid cycle that takes place in the matrix of the mitochondria now this this process called a glycerol 3-phosphate shuttle is used predominantly by skeletal muscle cells and this process allows the skeletal muscle cells not only to use the high-energy electrons to generate the much-needed ATP molecules but it also allows these skeletal muscle cells to actually regenerate the energy plus molecules needed to continue glycolysis now this actually is not the only type of shuttle that our cells can use and as we'll see in the next lecture liver cells and cardiac muscle cells actually use a slightly different shuttle system

Channel: AK LECTURES

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Keywords: glycerol phosphate shuttle, glycerol 3-phosphate shuttle, G3P shuttle, Glycerol 3-phosphate, glycerol 3-phosphate, transport of NADH molecules, biochemistry, glycerol 3-phosphate dehydrogenase

Id: sglxi7I21-M

Length: 14min 42sec (882 seconds)

Published: Fri Jun 12 2015