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0:01
hello and welcome to mel simplified in this video we will discuss about the krebs cycle I posted a brief video on the topic of Krebs cycle a few years back and that was a hugely popular video among you guys so this will be an update to that video in which we will discuss Krebs cycle in more detail but in a simplified way at least I'll try to so let's begin Krebs cycle is also known as a hands Krebs cycle or the citric acid cycle now hands after the scientists who discovered it hands
0:33
Adolphe Krebs in 1937 and received a Nobel Prize for Physiology and medicine in 1953 now this cycle is also known as a citric acid cycle after the molecule that plays the central role in kreb cycle the citric acid also known as the citrate the citric acid cycle is a key metabolic pathway that connects carbohydrate fat and protein metabolisms the TCA cycle is a central pathway into which many metabolites feed it consists of a number of reactions we generate nadh and fadh2
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which are in turn used to generate ATP's the krebs cycle consists of a series of chemical reactions that release stored energy of fats carbohydrates and proteins through the chemical process of oxidation other than being the central pathway for generation of energy the kreb cycle is also very important as it provides many raw materials that are used elsewhere in the body like amino acids and NADH an interesting fact about the Krebs cycle is that it was one of
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the earliest established components of cellular metabolism and may have originated a biogenic li meaning it originated even before the life started this is the concept of abiogenesis that the life originated from nonliving things get the lecture handouts from this video and all other videos on meth simplified join our community at patreon.com or click the join button below now before diving into all the chemical names the enzymes and the various steps of Krebs cycle
2:10
I would like to take a few minutes to talk about the conceptual basis of Krebs cycle that most teachers failed to explain so like I told you Krebs cycle is a central metabolic pathway now what do you mean by a central metabolic pathway now see when we eat food it is digested absorbed and is first processed by initial metabolic pathways these initial metabolic pathways generate some common products that are used by the central pathway like the Krebs cycle to produce energy like if we take the
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example of carbohydrates carbohydrates are digested into simple sugars like glucose and the glucose is first processed by initial metabolic pathways like glycolysis glycolysis produces pyruvate and similar products are produced by the initial metabolism of fats and proteins as well the pyruvate is then fed into the central pathway that is the Krebs cycle so the Krebs cycle provides a central pathway that connects carbohydrate fat and protein metabolisms
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now the next important concept is how does the kreb cycle produce energy for this let's take the example of metabolism of carbohydrates again we get simple sugars at the end of digestion of carbohydrates like glucose right and after this glucose under goes through all the metabolic pathways like glycolysis kreb cycle and electron transport chain one molecule of glucose produces approximately 36 ATP's but where does this energy come from the single body the answer to this question
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is through the chemical process of oxidation now see what happens is that through glycolysis and an additional reaction we break down glucose into small two carbon fragments which are known as acetate this acetate is then fed into the Krebs cycle if you look at the kreb cycle it consists of these ten intermediate molecules that start and end with citrate when we add acetate to this cycle this is a two carbon compound this cycle takes a full turn and releases two molecules of carbon dioxide
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as a waste product meaning the two carbons that we added in the form of acetate are released in the form of carbon dioxide this carbon dioxide is produced due to the process of oxidation that occurs in the Krebs cycle as a result of various enzymes electrons are added to nad to make nadh and fadh2 and are then subsequently used in the electron transport chain to make ATP through ionic gradients now all of this may seem a bit confusing in the beginning but my advice is to take
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things slowly was the other videos regarding glycolysis electron transport chain and metabolism of fats on our channel to have a complete understanding of this metabolic pathway the links to all these videos are in the description below meanwhile let's begin with the details of the krebs cycle and various enzymes involved so in eukaryotic cells the citric acid cycle occurs in the matrix of the mitochondria in the prokaryotic cells such as bacteria which lack mitochondria the citric acid cycle
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is performed in the cytosol
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now there is a very important reason why a CREP cycle takes place in the center of the mitochondria this is because of the presence of the electron transport chain in the membrane of the mitochondria this electron transport chain is a chain of many different enzymes that uses the products formed in the kreb cycle to produce energy in the form of ATP
6:01
now to learn more effectively about the Krebs cycle it is very important that you have a little bit of background knowledge about the preceding steps that happened before Krebs cycle so the kreb cycle begins with this molecule as a takeaway but where does this come from and what is its role in the kreb cycle this is very important to understand now one of the important biochemical pathways that runs before the kreb cycle is glycolysis in this pathway we break down glucose
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which is a six carbon compound into two molecules of pyruvate which is a three carbon compound what happens next is that this pyruvate is acted upon by a set of enzymes collectively known as a pyruvate dehydrogenase complex in this reaction coenzyme a is also involved which is a coenzyme derived from vitamin b5 in this reaction two carbons are transferred from the pyruvate to coenzyme a to form the acetyl co a one additional carbon present in the pyruvate is lost in the form of carbon
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dioxide in this reaction one molecule of NADH is also produced so this is how acetyl co a is produced from pyruvate this acetyl CoA is a two carbon compound and is the starting point of Krebs cycle in this molecule the coenzyme a the part which is derived from vitamin b5 acts just like a carrier which transfers the two carbons attached to it to the Krebs cycle so the first step of the Krebs cycle is the combination of acetyl co a with oxaloacetate like I told you
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acetyl co a is a two carbon compound and this two carbon compound combines with observe acetate which has four carbons this combination leads to formation of citrate which is a six carbon compound and this reaction is made possible by the enzyme citrate synthase the name of this enzyme is self-explanatory for what it does the citrate then undergoes a series of enzyme catalyzed reactions in which it loses the two carbons of acetyl co a in the form of two molecules of
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carbon dioxide the conversions which involve up to ten chemical reactions are all brought about by enzymes which use energy generated through oxidase to attach electrons to nad and fa D now let's look at what happens next with citrate in the next two reactions the citrate is converted into its isomer which is known as isocitrate both these reactions which I have shown with just one arrow are catalyzed by the enzyme equalities now this is an iron containing enzyme which reorganizes the
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atoms of citrate to form an isomer isocitrate now you may ask what was the need to convert citrate into isocitrate why can't the citrate just move forward with the pathway well the answer to that is that the arrangement of atoms in the isocitrate is better suited for the next few excision reduction reactions that are about to come in the Krebs cycle in the isomerization of citrate to isocitrate and intermediate is also generated which is known as sis Akane Tate but no need to go into the
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details of that moving on to the next step in the Krebs cycle in the next step the isocitrate is converted into alpha ketoglutarate by the enzyme isocitrate dehydrogenase now we come to the first of the for oxidation reduction reactions in the citric acid cycle these oxidation reduction reactions are the one which produce energy in Krebs cycle and all of these four reactions use enzymes in them which are known as dehydrogenases now what do these dehydrogenase is do and
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how do they produce energy that is very important for you to understand see if you look at the term itself dehydrogenase this literally means removal of hydrogen so dehydrogenases are basically enzymes that remove hydrogen from a molecule now as you remember that removal of hydrogen is also known as oxidation and the hydrogen that is removed from one molecule must be passed on to some other molecule the other molecule that receives the hydrogen gets reduced in return so this
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is the basic mechanism of action of dehydrogenases they remove hydrogen group from one molecule oxidizing it and in turn attaching that hydrogen group to some other molecule leading to its reduction this is why the reactions carried out by dehydrogenases are known as reduction reactions so coming back to our Krebs cycle we reached a point in crab cycle where isocitrate will now be acted upon by the enzyme isocitrate dehydrogenase so let's look at what happens in this reaction this is
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actually a two-step reaction in which the enzyme isocitrate dehydrogenase first removes hydrogen from isocitrate thus oxidizing it the hydrogen that is removed is attached to nad to form the NADH thus completing the process of oxidation and reduction but there is a small additional step that happens next which is catalyzed by the same enzyme isocitrate dehydrogenase in the next step of the reaction a carbon atom is also removed from isocitrate in the form of a molecule of carbon dioxide this
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leads to the formation of a 5 carbon compound known as alpha ketoglutarate so if you look at a complete chemical process that just happened here this is known as the oxidative decarboxylation oxidative because oxidation of isocitrate takes place since a hydrogen is removed from isocitrate and decarboxylation as a carbon group is also removed from isocitrate the conversion of isocitrate into alpha ketoglutarate is followed by a second oxidative decarboxylation reaction the
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formation of succinylcholine obliterate this reaction uses the enzyme alpha ketoglutarate dehydrogenase that catalyzes a similar oxidative decarboxylation of alpha ketoglutarate in this reaction also a hydrogen gets attached to nad to form the NADH since it is also a type of decarboxylation a carbon is removed from alpha ketoglutarate to be lost in the form of carbon dioxide also coenzyme a is used in this reaction therefore the product will be a combination that is known as succinylcholine
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in the next step of the kreb cycle the succinylcholine volted to succinate this reaction is catalyzed by the enzyme known as succinylcholine Thetis now try to understand what happens here in this reaction as this is a very important concept and often missed by many students the number of carbons remain the same in this reaction both 16 Alcoa and succinate have four carbons each so what changes 16 Elko is a high energy compound and the energy stored in this compound is used to attach an inorganic
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phosphate molecule to GDP this GDP gets converted to gtp which is like a close cousin of ATP and is later used in the formation of an ATP the coenzyme a attached to the succinylcholine in this reaction so what happens here essentially is that the succinylcholine uses its high free energy and it's coenzyme a to be converted into succinate and a molecule of gtp
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this is an example of substrate level phosphorylation a process of producing energy that we discussed in detail in our glycolysis video so now we have four carbon compound known as succinate in fact the number of carbons do not change from here onwards all the compounds which come next in the cycle only have four carbons the last compound generated in the cycle is oxaloacetate which also has four carbons and that of zero acetate combines with another molecule of acetyl co a to form
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citrate a starting point of the krebs cycle coming back to where we left the cycle so we have succinate which is a four carbon compound and it is acted upon by the enzyme succinate dehydrogenase as you can tell from its name this enzyme is a dehydrogenase so it removes hydrogen from succinate and the hydrogen that is removed is accepted by flavin adenine dinucleotide or fa d fa d is in turn converted to fadh2 succinate gets converted to fumarate fa d is the hydrogen acceptor in this
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reaction and not nad because attaching hydrogen to nad requires more energy then this reaction can provide so FA D is used here as it requires less energy change to get reduced to fadh2 energy change for four carbon compounds is less as compared to six or five carbon compounds that were present at the first half of the cycle there is however an exception to this at the end of the cycle that we will discuss in a bit now the enzyme involved in the conversion of succinate to fumarate is
15:21
succinate dehydrogenase which like equalities is an iron sulfur protein this enzyme is also very important as succinate dehydrogenase is directly associated with the electron transport chain the next step in the Krebs cycle is a hydration reaction which means we add a molecule of water to fumarate and convert it into malate this reaction is catalyzed by the enzyme fume arrays nothing special in this reaction so let's move on to the next one the next type of reaction that happens here is
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oxidation in which we finally oxidize malate to oxaloacetate and the enzyme involved here is again a dehydrogenase which is known as the malate dehydrogenase again the nad molecule gets reduced to nadh which will be used in the electron transport chain in this reaction nad gets reduced to NADH now you may ask why nad gets reduced here and not F ad because like I told you earlier that the free energy change for compounds in the end of the cycle is less as compared to that that was
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present at the first half of the cycle well this was the exception that I was talking about even though this reaction is present at the end of this cycle still a molecule of nad is getting reduced here well this is due to the fact that oxaloacetate that is being produced here is rapidly being utilized by combining it with acetyl co a to form citrate and the second product being produced here the NADH is also being rapidly used in the electron transport chain so the standard free energy for this
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reaction unlike that for the other steps in the citric acid cycle is significantly positive I know that some students especially in lower grades may find some of the concepts I explained here a little advanced but trust me you will have to learn about the cycle in depth at one point or another so better now the oxaloacetate again combines with a molecule of acetyl co a and leads to the formation of citrate with the help of the enzyme citrate synthase a water
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molecule is also added in this reaction but this completes one full turn of the cycle and the same sequence repeats again okay so if we look at the cycle now you can see that because what we got from this cycle we added two carbons to the cycle in the form of a molecule of acetyl co a these two carbons were released in the form of two molecules of carbon dioxide here and here in this process of oxidation and reduction we convert three molecules of nad to NADH one molecule of fa D to F ADH and we
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converted one molecule of gdp to GTP now there are few other important concepts regarding the kreb cycle that you must understand to have a complete knowledge about this biochemical cycle the first is this summary reaction of this cycle and the second is the energetics of the cycle meaning how many ATP's are produced for every one molecule of glucose that enters the cycle so first coming to the summary reaction of glycolysis now the net reaction of citric acid cycle is one molecule of
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acetyl co a plus three molecules of nad plus one molecule of F ad plus one molecule of GTP plus one molecule of inorganic phosphate plus two molecules of water combined to give two molecules of carbon dioxide and three molecules of NADH plus one molecule of GTP and one molecule of coenzyme a what is the gibberish well let me decode this reaction for you on the left-hand side of this reaction are the raw materials that are being used here and on the right hand side are the products that
19:11
are formed in the kreb cycle now in every single turn of the Krebs cycle we use one molecule of acetyl CoA that combines here with the absolvo acetate to form citrate three molecules of nad are used in the kreb cycle that get reduced to three molecules of NADH here you can see where the three nadh molecules are produced in the Krebs cycle 1 f ad molecule is used which gets reduced to one molecule of F ADH this fadh2 produced in the conversion of succinate to fumarate here 2 molecules
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of carbon dioxide are produced for every one molecule of acetyl co a that enters the Krebs cycle like i showed you earlier 1 coenzyme a is produced in the conversion of succinylcholine 8 where succinylcholine uses the coenzyme a and 1 molecule of gdp combines with one molecule of inorganic phosphate and leads to the formation of one molecule of GTP two molecules of water are consumed 1 in the synthesis of citrate and one hair in the hydration of fumarate okay so this was about the summary
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reaction of crap cycle now let's talk a little bit about how much energy is produced in the Krebs cycle most of the energy that is produced in the Krebs cycle is via the reducing equivalence the nadh and fadh2 are subsequently utilized in the electron transport chain if you look at the placement of these two pi o chemical pathways in the mitochondria they live very close to each other the krebs cycle operating in the matrix of the mitochondria and the electron transport
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chain in the membrane of the mitochondria so the nadh and fadh2 are being produced by the Krebs cycle are easily utilized in the electron transport chain for the production of ATP now the details of how these ATP's are produced in the electron transport chain and how many ATP's are produced are here in this video about electron transport chain on our channel in a nutshell you can remember that about 2.5 ATP's are produced by one NADH and 1.5 ATP's by one molecule of FA th
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like we discussed in the summary three nadh are produced through one turn of Krebs cycle and one NADH so three NADH and one fadh2 assign ATP's in total in electron transport chain plus we also have one ATP that is directly produced in the kreb cycle actually GTP is produced in the Krebs cycle here and this GTP is further utilized to convert an ADP to ATP directly thus one asset alkaway unit generates approximately 10 molecules of ATP through one turn of crap cycle since
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previously in glycolysis one glucose was split into two pyruvate which were further converted into two acetyl co a molecules which entered the Krebs cycle so 20 ATP's are produced per molecule of glucose in the Krebs cycle I hope you liked the video if you like our content make sure to support us so that we can keep making videos like this you can support us by joining a community on patreon calm or clicking the join button below by joining your channel you get exclusive content like
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handouts of this lecture and all other lectures on our channel flashcards behind the scenes of these videos early notifications exclusive posts and much more thank you so much for watching
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