in this lesson we're going to continue our discussion of dirty biochemistry by talking about the tca cycle as a quick refresher here's everything that we've talked about so far in the first video we talked about glycolysis and gluconeogenesis shown there in the red box when you go from glucose down to pyruvate you're undergoing glycolysis and when you go back up from pyruvate back to glucose you're going up doing gluconeogenesis in the next video we talked about the different options for pyruvate metabolism shown here in the red box remember there were four different options that pyruvate could take and one of those options was to convert pyruvate into acetyl coa and that is what we are talking about today acetyl coa can enter the tca cycle and undergo further metabolism to generate important molecules for future use in the electron transport chain today's video is about the tca cycle this is also known as the citric acid cycle or the krebs cycle the tca cycle has one main goal and it's important to keep the big picture in mind when we discuss it the goal is to generate nadh and fadh2 molecules the reason that you do this and we'll touch more on this at the latter stages of this video is to create molecules that can go into the electron transport chain and shuffle electrons to generate massive amounts of atp so again just for the purposes of keeping the big picture in mind the goal of the tca cycle is to generate nadh and fadh2 molecules so that those molecules can leave the tca cycle and go to another biochemical pathway known as the electron transport chain which we will discuss in another video to generate the most amount of atp now the overall reaction for the tca cycle is acetyl coa plus three nad plus plus fad plus gdp plus a phosphate and that yields two carbon dioxide molecules three nadh molecules one fadh2 molecule one gtp and one coa again look at the overall yield of the tca cycle we can generate three nadh and one fadh2 and that is the main goal of the tca cycle start with acetyl coa and again we started the video today talking about how pyruvate could be converted into acetyl coa and this marks the first step in the tca cycle acetyl coa will turn into citrate citrate will be converted into isocitrate so you just put an iso in front isocitrate will be converted into alpha-ketoglutarate and during this step you also have the production of one nadh alpha-ketoglutarate will be converted into succinyl coa and during this step you also have the production of one molecule of nadh succinyl coa will have the co-a ripped off and turned into succinate now it's during this step that the coa is produced again remember the overall net reaction of the tca cycle we are producing one molecule of coa and this is the step where that's done succinate gets turned into fumarate and during this step we have the production of our one and only molecule of fadh2 fumarate gets turned into malate and malate gets turned into oxaloacetate it's during this step that our third and final molecule of nadh is produced oxaloacetate can combine with acetyl coa and form citrate and the cycle can continue to spin so long as there is a stimulating factor in the body now let's pause for a second this is the overall biochemical pathway of the tca cycle it is not important to memorize every single enzyme that catalyzes every single step however the one that you do need to know is the rate limiting enzyme that rate limiting enzyme catalyzes the conversion of isocitrate to alpha-ketoglutarate so the rate-limiting enzyme of the tca cycle is isocitrate dehydrogenase now if you can memorize the actual stepwise pathway it shouldn't be hard to remember which step is catalyzed by isocitrate dehydrogenase because the name isocitrate dehydrogenase tells you which product or which substrate is being dehydrogenated so the enzyme is literally called isocitrate dehydrogenase so it's telling you that isocitrate gets dehydrogenated so therefore the conversion of isocitrate to alpha-ketoglutarate is the step where the rate-limiting enzyme of isocitrate dehydrogenase acts because again it's dehydrogenating isocitrate so your substrate for the rate limiting enzyme is isocitrate now that is the rate limiting enzyme and you absolutely need to memorize it but what also is important to memorize is what stimulates the tca cycle and what inhibits it adp will stimulate the tca cycle the reason is quite obvious the tca cycle's main goal again is to generate nadh and fadh2 now the purpose of that as i already stated is to have those molecules leave the tca cycle and go to the electron transport chain where they can be used to generate massive amounts of atp therefore in the presence of adp which is to say you don't have atp yet you're going to stimulate the tca cycle because the body wants atp and if the body wants atp it needs the electron transport chain and if it needs the electron transport chain then it needs the tca cycle to make fadh2 and nadh so the electron transport chain has the molecules it needs so again in the presence of adp you stimulate the tca cycle because you don't have atp and you're stimulating the tca cycle because you need fadh2 and nadh now obviously if adp stimulates the tca cycle then atp is going to inhibit it because think about it you don't need the electron transport chain and therefore the tca cycle if you've already got a lot of atp likewise nadh and fadh2 will have negative feedback and inhibit the tca cycle because if you already have them you don't need to make more of them this should be fairly obvious so please memorize what stimulates and what inhibits the tca cycle that's everything that's important as well as what stimulates and what inhibits the tca cycle but just for completeness sake i'm going to draw in the rest of the enzymes that catalyze this reaction citrate synthase is what makes cintrade a citrate and think about it the enzyme is literally called citrate synthase so it's synthesizing or synthasing citrate citrate goes to isocitrate that is done by aconitase alpha-ketoglutarate to succinyl-coa by alpha-ketoglutarate dehydrogenase again look at the name it's dehydrogenating alpha-ketoglutarate so obviously this enzyme works on the substrate alpha-ketoglutarate succinyl-coa goes to succinate from succinate thiokinase succinate goes to fumarate from succinate dehydrogenase again look at the name it's dehydrogenating succinate so it's obviously acting on succinate fumarate goes to malate from fumarase and ace means to break down so it's acing the fumarate or it's fema racing so it obviously acts on fumarate and then malate goes to oxaloacetate from malate dehydrogenase so if you look at the names of these enzymes it's rather simple and you know which enzymes go in here it doesn't matter if you know exactly where they go but if you know their names you know what they act on very very simple let's keep this simple keep the big picture in mind now something else that's high yield is to know again where the nadh is produced and where the fadh is produced and i've drawn them in here let's talk about nadh first so nadh starts with the letter n and all of the steps that produce nadh have reactants that are in the middle of the alphabet around the letter n so look at this i for isocitrate k for ketoglutarate and m for mallet they're all relatively around the letter n in the alphabet but look at where what the other steps begin with so citrate begins with the c that's in the very beginning of the alphabet so clearly that's not around the letter n oxaloacetate begins with the letter o and you know that's sort of around the letter n but it's you know classically thought of as the end of the alphabet so it's not quite right succinate begins with the letter s successional coe begins with the letter s that's too far back at the end of the alphabet so it's i k and m that generate the nadh now i understand that the letter o is technically close to the letter n but remember when you think about where the letter o is in the alphabet you classically associate it with the end of the alphabet but when you think about where the letter n and the letter m and the letter k and the even the letter i is it's kind of the middle so i know that's not a perfect mnemonic but it's something to help you remember where nadh is generated so again all of the steps that start with the letter that's around the letter n if you have to guess that's where the nadh is produced now as far as where the fadh is produced it's rather simple it's the equation or the the step that generates fumarate is going to be the one that generates fadh so the f's go together so where you form fumarate you form f adh2 and the f's just go together