If you're seeing this message, it means we're having trouble loading external resources on our website.

If you're behind a web filter, please make sure that the domains *.kastatic.org and *.kasandbox.org are unblocked.

Main content
Current time:0:00Total duration:11:49

Regulation of glycolysis and gluconeogenesis

Video transcript

at its most simplistic level regulation of metabolic pathways inside of the body it's really just a fancy word for a balancing act that's occurring in the body so to illustrate this I have a seesaw and we've been learning about two metabolic pathways glycolysis which is the process of breaking down glucose into pyruvate and gluconeogenesis which is essentially the opposite in which we start out with pyruvate and through a little bit of a different route we end up back at glucose and when we're talking about the regulation of these particular pathways we're essentially asking ourselves when is glycolysis the predominant pathway and one is gluconeogenesis the predominant pathway the body wants to make sure that we either have a net break down of glucose in the case of glycolysis or that we have a net production of glucose in the case of gluconeogenesis so now the next question is how does the body accomplish this balancing act and to answer this question the way I like to think about it is to think about it along a spectrum there are very fast-acting forms of regulation that take place on the order of seconds and there are very very slow forms of regulation that can take up to hours or even days to occur so let's talk about each of these in a little bit more detail the major principle that helps me understand fast-acting forms of regulation is a good old principle from general chemistry the shot liaised principle so if you remember the Shelia's principle talks about anything that's in equilibrium and it says that if there's any change to this equilibrium let's say more products are added or reactants are taken away the equilibrium will adjust to essentially counter that change and return the system back to equilibrium so what does this mean in the context of metabolic pathways like glycolysis and gluconeogenesis so let's remind ourselves that in glycolysis glucose is converted to pyruvate through several reactions that are kind of all in equilibrium with one another and so we can essentially think about this metabolic pathway as a series of equilibria and so imagine for example if we had an influx of glucose let's say we've just seen a big meal and a huge bunch of glucose has entered our body in our bloodstream what will happen to this equilibrium while we can return to the Shelia's principle and say that if we have a rise in glucose it will essentially push this entire equilibria towards the production of pyruvate and so you can see that in this example is Shotley principle allows equilibrium to adjust within seconds to just a simple influx of glucose to promote glycolysis the shelley's principle also applies to gluconeogenesis so remember that in gluconeogenesis something unique starts to happen after blood glucose levels have been low for a while amino acids begin to break down and form this metabolite called ox low acetate and remember that oxaloacetate plays its unique role in the conversion of pyruvate back to glucose which occurs in gluconeogenesis remember that it's kind of this intermediary the pyruvate is converted to oxaloacetate and then essentially re-enters the equilibria to form glucose so you can imagine that if we have an influx of oxaloacetate the equilibria will be pushed towards the opposite direction that is towards the production of glucose now in addition I want to briefly mention another form of fast-acting regulation which is called allosteric regulation so what is allosteric regulation recall that all metabolic pathways have unique enzymes that catalyze or facilitate each step of the reactions along the metabolic pathways so you can imagine that if we have an enzyme here I'm just drawing a simple structure it has what's called an active site where it actually binds the substrate of interest so it binds the let's say glucose molecule here but in addition there are also molecules within the cell that we call allosteric right you laters and these by definition bind to a portion of the enzyme that is not the active site so let's say we have an allosteric molecule that binds to a separate portion like right here now this allosteric molecule can have one of two effects we say that allosteric molecules can be inhibitory that is by inhibiting enzymes inhibit the pathway that utilizes those enzymes or these allosteric interactions can be positive that is promote the action of enzymes and therefore promote the overall reaction in which those enzymes are involved so to put this in context with glycolysis and gluconeogenesis above it turns out that ATP is actually a big allosteric regulator of one of these two pathways so recall that gluconeogenesis requires ATP out a net amount of ATP to produce glucose it's an anabolic building up pathway on the other hand in glycolysis there is a net release of ATP and the oxidative breakdown of glucose and so if we have a lot of ATP in a Cell think about for a moment which of these two pathways would be favored indeed gluconeogenesis would probably be favored because it requires ATP on the other hand if there's a lot of ATP that's kind of assigned to the cell to say hey we don't need to perform as much glycolysis because we already have enough ATP available and it does turn out that ATP is actually an allosteric regulator of a couple enzymes in glycolysis and specifically it's a negative allosteric regulator or an inhibitor of these couple enzymes essentially it's putting the brakes on glycolysis and saying we have enough energy and we don't need to produce any more on the other hand it turns out that there is also a molecule a MP in the body which is basically a sign that the cell has used up all of its ATP in other words ATP has been D phosphorylated and turned into a MP which is a sign that that cell is running out of ATP so if the cell is running out of ATP the cell probably will want to be performing energy-requiring processes such as gluconeogenesis and indeed a MP is a negative allosteric regulator of one of the enzymes in gluconeogenesis all right so that kind of finishes up our discussion of fast-acting forms of regulation so now let's talk briefly about slow-acting forms of regulation so these types of regulation often take advantage of transcriptional changes within the cell so what do I mean by that so let's first remind ourselves what transcription is to remember that transcription is the process of taking DNA and making an mRNA transcript and then translating this in the cytosol of the cell to a protein product and when we're talking about proteins oftentimes we're talking about enzymes so I'm just going to go right write that here since it's relevant for our discussion and so you can imagine for example that this might be very useful if the organism is in a long-term fasting state it will want to essentially up regulate the transcription of enzymes that promote something like gluconeogenesis so that it can dump glucose into the blood and notice here that you know even visually as its implied carry this process of going from DNA to mRNA to enzymes is going to take much longer than you know a simple Shotley a or allosteric regulation and so that's why this process is more of an adaptive process that allows the organism to adapt to more of kind of long term changes that it experiences in its environment now finally I want to add in one more form of regulation between fast and slow action regulation which is called hormonal regulation so what is hormonal regulation well it's exactly what it sounds like it's the ability for the body to essentially produce specific hormones which are simply molecules that travel in the blood to regulate whether glycolysis or gluconeogenesis is on or off and the two wormans that the body uses to regulate glycolysis and gluconeogenesis and pretty much actually all metabolic pathways are insulin and another hormone call glucagon and depending on whether there is more insulin or more glucagon the body will be more likely to do glycolysis or more likely to do gluconeogenesis so let's talk about how that decision is made now hormones like insulin and glucagon are usually released by the body whenever the body deviates from a particular set point now in the case of regulation metabolism a set point that we're interested in is the blood glucose level and if we return back to our analogy here this seesaw here this kind of pivot point we can kind of think about as our setpoint the blood glucose level is a specific amount of glucose that the body wants to have in the blood at all times not to get more specific if the blood glucose level rises it actually stimulates the body to release the hormone insulin and if the blood glucose levels decrease it stimulates the body to release the hormone glucagon and so with that in mind take a moment to think about which hormone insulin or glucagon promotes glycolysis and which of these two hormones promotes gluconeogenesis basically this is actually a macro application of Wasabi's principle right if we have too much blood glucose level we want to get rid of it how do we get rid of it we break it down and so indeed insulin promotes the glycolysis on the other hand when blood glucose levels are low we want to return the equilibrium to normal we want to pump more glucose back into the blood and we know that gluconeogenesis can accomplish that for us and so glucagon indeed promotes gluconeogenesis now briefly at the end I want to talk about why I decided to put hormonal changes between fast and slow acting forms of regulation so to talk about this we need to understand a little bit how hormones interact with target cells so cells in our body have particular receptors that will bind to the hormones that are floating around in the bloodstream so once these receptors bind to a particular hormone whether it be insulin or glucagon it actually causes a series of particular reactions to occur inside of the cell to modify oftentimes Symes that are involved in metabolic pathway so I'll just abbreviate that with a letter e and these modifying reactions that occur in the seller oftentimes phosphorylation reactions that is either the gain or the loss of a phosphate group oftentimes on an enzyme in a metabolic pathway and so with that in mind you can appreciate how modification by phosphorylation is a lot faster than starting with a DNA transcript and then going to mRNA and then and then translating it to enzymes but it is indeed a bit slower than kind of a second a second with Shotley a and allosteric regulation that can occur in a cell as well