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Gluconeogenesis: the big picture

Video transcript
- [Instructor] What I think is pretty fascinating is our body is able to maintain a very narrow and constant range of blood glucose in our body so noticeably about 60 to 150 milligrams of glucose per deciliter of blood and it's not important that you know this exact number but what I think is significant is it contrasts something like free fatty acids for example, which we'll talk about in fatty acid metabolism. Fatty acids can range almost tenfold depending on the needs of the body so they can be very high or very low but glucose always stays within a constant range, blood glucose level here, and it's important that this is a very constant range because there are some tissues in our body such as our brain, some of the cells in our eyes, and our kidneys, and even our red blood cells that rely on glucose nearly exclusively to produce ATP. So remember once glucose is in the blood, it can be used by any of the cells in our body by process of cellular respiration to produce ATP. Remember the three big steps of cellular respiration are first glycolysis, the breakdown of glucose, and then the glucose goes to the Krebs cycles where it undergoes some more oxidation to release all of that energy in the glucose molecule, and finally the byproducts of glycolysis and the Krebs cycle go to the electron transfer chain which is able to produce ATP in bulk amount. So how does our body keep this blood glucose in such a narrow range and constant range in our body? Our body is able to do this differently depending on what state the body is in, so the body can be either in the FED state or something we call a fasten state. You can imagine the FED state just after you've eaten a meal. So let's say you've eaten a chocolate chip cookie. The glucose that has been broken up in your GI tract can then be used to directly contribute to this blood glucose level and then of course the glucose can be used by our cells. Now in the fasten state, this is all the times your body is not eating, the body has come up with two different ways to regulate blood glucose levels. Remember in the fasten state, our body needs way to pump glucose into the blood to keep it at this level, essentially to replace the glucose that's being used by our cells because we don't have this constant intake from our chocolate chip cookie. In this case our body has glycogen, which is a polymer, or a string of glucose molecules that it stores away. Our body ingeniously makes this glycogen by using some of that glucose that is dumped into our body during the FED state, so in anticipation of knowing it's not always going to get glucose from eating, it preserves some of it in this glycogen molecule, and most of this glycogen molecule is located in your liver which is why your liver is very important for carbohydrate metabolism. In times of fasting, our body can actually go ahead and break down this glycogen into the individual glucose molecules which then can be used to keep our blood glucose levels constant. Unfortunately it turns out that this method of breaking down glycogen only lasts for about 10 to 18 hours in our body, that is to say after 10 to 18 hours we've used up our glycogen stores and we need to eat another meal to build those glycogen stores back up. You can imagine during an overnight fast for example, it's usually about hopefully eight to 10 hours. You can imagine there is a point during the day where your body needs another way of producing glucose. Our body has come up with a second way called gluconeogenesis, which is indeed the topic of this video. Gluconeogenesis is exactly what its name implies. It is the genesis of creation of neo, new, glucose. It's actually fascinating to think about this for a moment. What we're saying in gluconeogenesis is our body is taking precursor molecules that are from a non-carbohydrate source, so looks at what it has lying around and most commonly it uses amino acids in our body as well as a molecule called lactate which is produced as a byproduct in exercising muscle cells, and it takes these precursor molecules and reconfigures them to produce glucose and it's this glucose that can then be used to be dumped into our blood to maintain constant blood glucose concentration and a constant supply of ATP for our tissues. Now that you have a big picture of carbohydrate metabolism and where gluconeogenesis fits in, let's go ahead and talk about this metabolic process, gluconeogenesis. In order to do this, it's actually important to revisit glycolysis briefly so I'm gonna go ahead and bring up the reaction diagram that was used to explain glycolysis in a previous video. Just to orient you, remember that glycolysis begins with glucose up here and glucose is broken down in a series of steps. Most notably it's broken down into this three carbon molecule, glyceraldehyde three phosphate and then it is broken down even further and reconfigured, releasing some ATP and ADH along the way and ultimately releasing this molecule pyruvate and pyruvate is a very important molecule because it can continue to the Krebs cycle where it can be further oxidized to produce more NADH that can be used by the electron transfer change to produce ATP. Alright, so that was a big mouthful. Just remember, big picture, glycolysis breaking down glucose into pyruvate. Turns out, the way I like to think about gluconeogenesis is that the goal of gluconeogenesis is to produce glucose and so, gluconeogenesis is almost the exact reverse pathway of glycolysis. We start at this end of the reaction pathway, we start with pyruvate, and we go funnel back the opposite direction through all of these reactions to produce glucose. Now the key word is that it's almost the exact reverse of glycolysis and it's almost the reverse because I want to call attention to these orange arrows so note that there are three orange arrows, so one from glucose to this molecule glucose six phosphate, another one here, and then one at the very end which converts the last molecule to pyruvate. What's important to note about these reactions in glycolysis is that, unlike the other bidirectional black arrows that are used in most of the reactions, these orange arrows are unidirectional. What they're trying to indicate is that these three reactions are irreversible. In other words, they have a negative, if we pull out a fancy term from chemistry, they have a negative delta g value, or a negative Gibbs free energy which means that if we were to reverse these particular reactions we would have to flip the sign, so these negative delta g values would be become positive and that's problematic because we know that for any biological reaction to occur we must have a negative delta g value. So our body has come up with a compromise. Our body has said we have one, two, three, four, five, six, seven reactions which these bidirectional black arrows which are essentially reversible, that is to say they have a delta g value that is near zero and so they can go either direction. Our body says we'll keep those seven reactions but I'm going from pyruvate back to glucose we have to come up with a different reaction pathway for the three steps that are irreversible so that's exactly what our body did. In fact, I'll go ahead and review in the remainder of this video but you can say, with those three steps in mind, we're just performing the reverse of glycolysis.