Professor Dave again, let's talk about the citric acid cycle. We learned about glycolysis, which is an anaerobic process, meaning it does not require oxygen to occur. Since oxygen is not necessary, the first simple organisms on earth were able to generate energy through glycolysis for millions of years. But two ATPs per glucose just isn't that much. In order for higher organisms like animals to evolve that can run, and jump, and swim, they had to evolve additional metabolic pathways that generate far more energy than glycolysis. This became possible once plants covered the earth, thereby filling the atmosphere with oxygen, which is a product of photosynthesis, thus the possibility for large-scale oxygen dependent aerobic respiration was born. The location in the cell where this process occurs is the mitochondria, which are eukaryotic cell organelles. According to endosymbiotic theory, mitochondria seem to have been entirely separate organisms that were incorporated into eukaryotes specifically for the respiratory abilities they possessed. This activity begins with the pyruvate molecules that were generated in the cytoplasm during glycolysis. These pyruvates will enter the mitochondrial matrix to find Coenzyme A. In the presence of NAD+ pyruvate will undergo decarboxylation, oxidation by NAD+, and then attachment to Coenzyme A, generating acetyl CoA. Acetyl CoA will then enter the citric acid cycle, also known as the Krebs cycle, or the tricarboxylic acid cycle. This is an eight-step pathway requiring eight separate enzymes. In the first step, the enzyme citrate synthase removes the acetyl group and tacks it on to oxaloacetate to form citrate. Next, with help from aconitase, a water molecule is removed and another one is added to generate a structural isomer of citrate called isocitrate. Then, catalyzed by isocitrate dehydrogenase, isocitrate is oxidized by NAD+ and then decarboxylates to form alpha-ketoglutarate. Next, another CO2 is lost and further oxidation by NAD+ takes place, with the help of ketoglutarate dehydrogenase. The resulting molecule will join with Coenzyme A once again to form succinyl-CoA. CoA is then displaced by a phosphate group to form succinate, which is catalyzed by succinyl-CoA synthetase. This will make one molecule of guanosine triphosphate, or GTP, in the process, which can be used to make one ATP. Then with the help of succinate dehydrogenase succinate is oxidized by a different molecule, FAD, which will result in fumarate and FADH2. Next, fumarase will catalyze hydration which results in malate, and lastly, one more oxidation by NAD+ takes place with the help of malate dehydrogenase to give oxaloacetate, which will restart the cycle, reacting with a new acetyl CoA. Overall, for every acetyl CoA that enters, this cycle will produce three NADHs, one FADH2, and one ATP. Since one glucose will produce two pyruvates in glycolysis and therefore two acetyl CoAs, we can double these numbers to get the amounts per glucose molecule. Once again, for the ease of memorization, here is a list of each step of the citric acid cycle with the names of the respective enzymes. We can see that there still hasn't been a huge payoff in terms of energy, but the products of the citric acid cycle will then move on to oxidative phosphorylation, which will generate the majority of the ATP produced in aerobic respiration. Thanks for watching guys, subscribe to my channel for more tutorials, and as always, feel free to email me: