Glycolysis

welcome back to the high-yield biochemistry series this is brought to you by dirty medicine in today's video we're going to continue our discussion about the biochemical pathways and talk about glycolysis glycolysis is typically the first biochemical pathway that you learned when you're learning about biochemistry and it's because of that that it's extremely high yield shows up on exams all of the time now when you're learning about glycolysis as you'll see me mentioned throughout this video it's really important to remember the bigger picture and when I say that I'm referring to things like what is the

function of the role of glycolysis what are we taking as a reactant and turning into a product and what are the regulatory mechanisms in terms of feedback so what makes this go forward what inhibits this and what is the rate-limiting enzyme just like all of the biochemistry videos that I've created you need to know the rate-limiting enzyme and the regulatory mechanisms so we're talking about things like inhibitors etc so let's start with a quick overview of glycolysis glycolysis is an irreversible biochemical reaction that occurs in the cytoplasm the net equation for glycolysis is that you

start with glucose and the goal is to take that glucose and turn it into pyruvate where it can downstream take multiple pathways through that pyruvate pathway and preferentially usually this goes into the citric acid cycle but here's the net equation you've - you start with glucose and you add two phosphates two ATP's and two and a DS and what you get out of that is two pyruvates plus two ATP's plus 2 NADH plus two hydrogen's plus two waters but if you wanted to just think very simply about what glycolysis is doing it's taking glucose and

breaking that glucose down into storable products that the body can use in other biochemical pathways so now that we've understood the overview of glycolysis let's just get to the the meat and potatoes here we're gonna talk about the pathway you need to understand the pathway and I'm gonna pay very special attention to the regulatory mechanisms of this pathway and the rate-limiting enzyme so you start with glucose right any person takes a bite of a cheeseburger eats a french fry drinks a milkshake and they've got a bunch of carbohydrate in their body and that carbohydrate is

composed usually of glucose and if it's not of glucose then the other types of sugars will get turned into glucose so that glycolysis can utilize it the first step is glucose will get turned into glucose 6-phosphate glucose 6-phosphate will get turned into fructose 6-phosphate fructose 6-phosphate will get turned into fructose 1 6 bisphosphate and now you've got like multiple steps that are gonna happen there's gonna be four or five more reactions in this pathway and you'll end up with phosphoenolpyruvate which will get turned into pyruvate and going from glucose down to pyruvate is the entire

glycolysis pathway so when you get to pyruvate you're basically finished with glycolysis now let's talk about the important enzymes that you need to know so the first step that converts glucose to glucose 6-phosphate there's actually two different enzymes that can be used depending on the circumstances of the glucose concentration and where in the body we're talking about so those two enzymes are glucokinase and hexokinase so to be perfectly clear either glucokinase or hexokinase can convert glucose to glucose 6-phosphate and what you'll need to know for test a that's really high yield is to understand under

which circumstances both of these enzymes might be used so for gluco kinase this enzyme has a low affinity and a high km just remember the reciprocal relationship between affinity and km the higher the km the lower the enzyme has an affinity for its substrate so glucokinase has a low affinity for glucose it typically doesn't want to go and grab glucose and the reason for this is because glucokinase acts as a glucose sensor its present in the liver and the pancreatic beta-cells and it's only used when glucose is at high concentrations so basically what you should

think of glucokinase s is an emergency enzyme that is acting as a glucose sensor and it's really not grabbing glucose because instead of grabbing glucose and breaking it down through glycolysis what it's doing is it's sensing glucose and it's going okay let's test how much glucose is over here and that's okay we're not gonna jump in yet HECO kinase you go first so hexokinase on the other hand that is a high affinity enzyme which means it has a low km and because it has high affinity for its substrate hexo kinase is the one that's constantly

going to be latching on to glucose and converting it to glucose 6-phosphate and sending it down the glycolysis pathway and the reason for that is because hexo kinase is the enzyme that's used to operate the basal glucose metabolism so constantly throughout your body in all of your tissues you have this enzyme hexokinase that's just keeping a basal level of glucose metabolism present it's trying to make sure that your glucose level is adequate throughout the body in all of the tissues but if hexokinase becomes overwhelmed because suddenly there's a massive influx of glucose that is when

hexa kinase turns to glucokinase and says gluco i know you usually have a low affinity but i really need some help now because the glucose concentration is high so if you think about it that's the reason that glucokinase is only found in the liver and the pancreatic beta-cells because it does a very specific regulatory job where it's only acting when the blood glucose levels are super super high when that concentration reaches some critical point that's when glucokinase in the liver and the pancreatic beta-cells jumps in to save hexokinase so the takeaway from this slide is

that both glucokinase and hexokinase are enzymes that catalyze that conversion from glucose to glucose 6-phosphate the only difference is that hexokinase is kind of there all of the time making a basal level of glucose and glucokinase jumps in in emergencies but understand the differences between those two enzymes that I've put in the gray boxes they are extremely high yield and probably will show up on your test so here's where we are we've we've talked about the enzymes in the first step the enzyme that converts fructose 6-phosphate to fructose 1 6 bisphosphate is the rate-limiting enzyme

of glycolysis and that's phosphofructokinase 1 sometimes you'll hear this referred to as PF K 1 so PF k 1 or phosphofructokinase 1 is the rate-limiting enzyme and it converts fructose 6-phosphate to fructose 1 6 bisphosphate now I told you at the start of this video that the very important thing to keep in mind for USMLE and comlex is the regulatory mechanisms and what I mean when I say regulatory mechanisms are what inhibits this pathway and what promotes this pathway and we're going to talk about that for the first time right here and because phosphofructokinase 1

is the rate-limiting enzyme it's really high yield to understand what inhibits phosphofructokinase 1 and what promotes phosphofructokinase 1 and that's what you see here so ATP and citrate will inhibit the rate-limiting enzyme pfk one but a MP will promote the rate-limiting enzyme of pfk 1 and this should be somewhat intuitive to you so so think about what glycolysis is doing the role of glycolysis is to take glucose convert it to pyruvate and ATP and then let that pyruvate enter one of many different pathways but usually the citric acid cycle where you'll then create citrate so

if you think about that the question becomes what would this pathway want to do if it already had ATP and therefore didn't need to make it or if it already had citrate and therefore didn't need to make pyruvate which would then go to citrate and that's why ATP and citrate inhibit pfk one because if you have ATP and you already have citrate then you don't need to do glycolysis so the presence of those products will inhibit the rate-limiting enzyme and therefore glycolysis won't occur now likewise think about AM P if you have AM which is

mono phosphate only one you don't have ATP and therefore if you don't have ATP you want to do glycolysis so in the presence of a MP which is to say in a situation where you don't have ATP a MP will promote PF k1 and will therefore promote glycolysis so anytime you're not really sure about how the regulatory mechanisms are working think about this intuitively ask yourself on test say well would glycolysis happen if there was a MP would glycolysis happen if there was citrate it should make sense to you if you understand what the big

picture role of these pathways are so that's what promotes and inhibits pfk one now I need to pause for a second and tell you about this little nuance of glycolysis so fructose 6-phosphate can can go to fructose 1 6 bisphosphate as you see on this slide but additionally there's sort of a side step that occurs a pivot if you will fructose 6-phosphate can also become fructose 2 6 bisphosphate and if fructose 6-phosphate will become fructose 2 6 bisphosphate the enzyme that catalyzes this conversion is phosphofructokinase 2 pfk 2 so very similarly named of course to

the rate-limiting enzyme that we just talked about but instead of one it's two so when this happens you create fructose 2 6 bisphosphate and interestingly that fructose 2 6 bisphosphate will promote pfk 1 so the goal when the body does this is to make glycolysis happen faster now the question then becomes what is promoting or inhibiting phosphofructokinase 2 or pfk 2 and that's really simple so it's gonna be inhibited by glucagon and it's gonna be promoted by insulin so think about it if fructose 2 6 bisphosphate makes glycolysis happen faster and in glycolysis you're breaking

down glucose it makes sense that insulin will promote pfk 2 because in the presence of glucose the body's gonna secrete insulin and the body's telling anything that any cell that has a glycolysis pathway occurring it's like yo take that glucose break it down please get this out of the system and that's insulins roll the opposite of that is glucagon glucagon is putting the brakes on this pathway and saying yo chill we need to reverse this and make energy available because blood glucose is low so think about it guys insulin will promote pfk to because it

will make fructose to 6 bisphosphate which feeds back to PF k1 and makes this happen faster but in another situation glucagon will inhibit pfk too because PF k2 would normally make fructose 2 6 bisphosphate which would feed back to PF k1 and make this process happen faster so again understanding the big picture about what glycolysis is actually doing helps you understand the regulatory mechanisms that you need to memorize for your test so the takeaway from this slide is that PF k2 inhibited by glucagon and promoted by insulin the last enzyme that we need to talk

about is the enzyme that converts phospho enol pyruvate to pyruvate the last step of glycolysis that enzyme is pyruvate kinase and just like pfk one this is going to be inhibited by ATP and citrate for the same exact reasons and those reasons are again glycolysis wants to create ATP glycolysis wants to make pyruvate which can then become citrate in the TCA cycle so therefore if you already have ATP or you already have citrate what's the point you don't need to do glycolysis so the presence of those products will inhibit the enzymes that usually make like

pollicis work so guys that's it for glycolysis and you're probably sitting there I started to have a panic attack thinking about whoa whoa dirty what about all the other enzymes don't don't worry about the other enzymes this is what you need to know for USMLE and comlex you need to know the enzymes I put in these slides the regulatory mechanisms that I put in these slides and understand the difference between glucokinase and hexa kinase that we discussed at the beginning of this video all of the other intermediary steps you don't need to know them you

really don't they're not going to show on your test unless you're taking a college-level or intro to biochemistry course you really don't need to know them if you do want to know them for completeness sake I would encourage you to go online look at some diagrams memorize some enzymes but this is what you need to know to answer 99% of the questions that'll show up on us Emily complex your question banks your practice tests etc so again and I cannot stress this enough because it's the biggest theme for all of biochemistry no the rate-limiting enzyme

no the regulatory mechanisms and if you get stuck on test day about what's inhibiting or what's promoting ask yourself what's the goal of this pathway and therefore what do I think might happen that's it if you liked this video drop me a like or a comment in the comments section please remember to check my patreon page you can click that link in the description of any of my videos sign up to send a secure monthly donation and support the channel love you good luck