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Current time:0:00Total duration:9:44

Gluconeogenesis: unique reactions

Video transcript

alright so in the previous study we talked about the big picture of gluconeogenesis or the creation of a new glucose and I brought up this diagram of glycolysis and I said to you essentially glycolysis which starts off with glucose that you can see in the kind of top metal left and is broken down oxidized into pyruvate the molecule kind of in the top left there I said that this pathway is essentially the reverse of gluconeogenesis that is to say we want to start off with pyruvate and we want to essentially reverse the pathways to produce glucose which we can pump into our blood in times of fasting but notably in this video and get a little bit more detail oriented and talk about kind of three unique reactions to gluconeogenesis that overcome the three irreversible steps indicated by the orange arrows in this diagram of glycolysis all right so let's talk about the first roadblock that we need to overcome which is in the conversion of pyruvate to fossil you know pyruvate so remember it can't just use pyruvate Tiny's to reverse this reaction so it actually uses an entirely separate set of enzymes and pathway to get to fossil enol pyruvate and the first step is a conversion of pyruvate to a molecule called oxaloacetate which is abbreviated usually as oaa and this is a molecule that you will meet when you learn about the krebs cycle it's a intermediate in one of those steps and notably this is why amino acids are able to be used to produce glucose because amino acids once they're broken down can be actually converted to oxaloacetate and from there of course they can continue down this pathway notably another precursor molecule that I mentioned before lactate can be interchangeably produced from pyruvate or going from lactate to pyruvate that's another way that that metabolite contributes to gluconeogenesis but back to oxaloacetate so once this is produced oxaloacetate can then be catalyzed to form faso enol pyruvate using another end I'm and the names of these enzymes aren't terribly important but I will mention them because they do sometimes come up so the first step involves an enzyme called pyruvate carboxylase and notably kind of one way that I remember this is because oxaloacetate is actually a four carbon molecule so pyruvate recall is a three carbon molecule so this carboxylase enzyme is essentially adding another carbon through a carboxy group to this ox lo acetate molecule and then this ox lo acetate molecule is converted back to a three carbon intermediate by an enzyme called PEP which stands for phospho enol pyruvate for short PEP is converted by PEP carboxy kinase and of course kinase involves the phosphorylation of something and so we know actually intuitively that because gluconeogenesis is an anabolic process we're building something up it requires energy and energy comes usually in the form of ATP and turns out that this first step of the reaction does involve ATP so I'm going to say plus ATP and the second step where this kinase is involved also involves energy in the form of GTP which is pretty much the equivalent of ATP but of course we have this G which is just guanine a different nucleotide base but this course we know the energies derived from these phosphate groups so essentially we can think of these things as being the same alright so one roadblock down into left to go so once we have our phosphoenolpyruvate we're good to go we shuttle down this pathway until we hit our next roadblock which is in the conversion of fructose 1 6 bisphosphate to fructose 6-phosphate so the way our body does this is actually use a different enzyme so know Emily phosphofructokinase is used to convert fructose 6-phosphate to fructose 1 6 bisphosphate and instead in gluconeogenesis it's going the opposite direction the body uses an enzyme called fructose 1 6 so we're talking about the same molecule here but instead of kinase we're using a by phospho taste it's kind of a mouthful but just recognize that a phosphatase is the exact opposite of a kinase so where as kinase is involve phosphorylation usually using phosphate groups from molecules like ATP a phosphatase takes these phosphates away so naturally it makes sense that if a kinase is used in going from fructose 6-phosphate to fructose 1 6 bisphosphate we'd want to take a phosphate group off going the opposite direction that so that's exactly what we do now one kind of point of confusion that kind of I had when I was learning this was you know we always learned that the enzyme of your reaction can't really change where the reaction is irreversible or not so I want to point out that it's not just an enzyme that we're switching out and going and kind of in circumventing this irreversible reaction because that really wouldn't do anything if a reaction has a negative Delta G value it will always have a negative Delta G value and changing the enzyme won't change the Delta G value remember kinetics and thermodynamics are separate entities and so I want to point out to you that it's really this entire reaction pathway that's changing and notably notice remember that ATP in this step is hydrolyzed to adp and this reaction is coupled normally to the phosphorylation with the enzyme phosphofructokinase but this hydrolysis of ATP is absent in gluconeogenesis so we can essentially think about this switch and enzyme as really encompassing a larger change in the entire pathway going from fructose 1 6 bisphosphate - fructose 6-phosphate so I hope that's clear so now we have gotten past this second roadblock we continue down until we hit our final and last roadblock and going from glucose 6-phosphate to glucose and again just essentially just like we did for a previous reaction our body has come up with a different reaction pathway involving a different enzyme so normally remember hexokinase is used in converting glucose to glucose 6-phosphate but our body uses a different enzyme in this case I'm going to write it out here it uses the enzyme glucose 6 and remember if we use 2 kinase we have to be using a exactly we're using a phosphatase so glucose-6-phosphatase which will remove this phosphate group from the glucose to remove its phosphate group from the glucose 6-phosphate to form the glucose now just as a fun kind of intriguing fact it turns out that some people are actually missing this enzyme glucose-6-phosphatase so can you imagine what would happen if they're missing this enzyme and indeed without this enzyme we can't produce glucose so it's kind of sad right because those individuals can perform all of these reactions leading up to glucose 6-phosphate but it can't ever produce glucose and what's actually even more interesting about this enzyme as this enzyme is also used in the breakdown of glycogen which if you remember we mentioned earlier as that polymer of glucose that's used kind of at the first line dumping mechanism for glucose into the blood during our fasting state so not only are these individuals unable to produce glucose using gluconeogenesis but they're also unable to break down their glycogen which means that they're severely hypoglycemic so without this enzyme go ahead arrow and cross it out without this enzyme individuals are hypo or low in glucose and of course is a very life-threatening condition because our body needs glucose to survive alright so just kind of as one final word I want to say that when I was first learning about gluconeogenesis and glycolysis I wanted to memorize all of the names of all the molecules and all the enzymes and speaking of enzymes I think I spelled one wrong here this is supposed to be 1 6 bisphosphate but despite that really I guess the key point I want to say is that you know these names can be important when we're talking about specific diseases like this deficiency of glucose-6-phosphatase but conceptually it's I think enough to realize at this point that gluconeogenesis and glycolysis are essentially opposites - these three irreversible steps for which our body has created 3 unique reaction pathways for which like gluconeogenesis can occur so that's kind of the big big takeaway from this video