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Alrighty, round two of sugar metabolism: the Citric Acid Cycle, also known as the Krebs Cycle or the Tricarboxilic Acid Cycle.  Just like my previous post, we’ll run through the cycle stepwise, indicating enzymes and reversibility as well as any other notable information.  Lets get crackin’!

The TCA Cycle: An Overview!

Its a lovely circle!

Big sucker, yeah?Step 0: First, before the cycle can begin, we must take pyruvate (from the results of our glycolysis) and transform it into acetyl-CoA in order for the cycle to legitimately begin.  To do so, pyruvate dehydrogenase takes CoASH and NAD+ (with the help of the coenzyme TTP) and binds CoASH as acetyl-CoA, while giving off NADH and H+. (The NAD+ is used as a cofactor to return the enzyme to its original state) Now we can begin the TCA cycle.

Citrate Synthase in action!Step 1: Acetyl-CoA is added to oxaloactetate to make citrate, which adds a carbon to the chain, making it 5 carbons (instead of oxaloacetate’s 4), as well as transforming several of the groups on the carbons.  I will not go into detail here to spare you all the pain, but instead provided an image of the transformation. CoAsH is removed. This is irreversible.

Step 2: Citrate is then transformed into isocitrate by moving the OH group on C3 to C4.  Aconitase catalyzes the reaction and it is reversible.

Step 3: Isocitrate then has the newly moved OH group dehydrogenated to a carbonyl group, as well as has the COO- group from C3 removed entirely (with two H’s added in its place).  This compound is called a-ketoglutarate and it is catalyzed via isocitrate dehydrogenase.  The reaction is not reversible as NAD+ is reduced to NADH and CO2 is formed.

Step 4: A-ketoglutarate then has CoASH added yet again, this time to replace the COO group at C5 to form an SCoA group (Succinyl CoA the whole compound is called).  A-ketoglutarate dehydrogenase catalyzes the reaction, which is irreversible.  It takes NAD+ and CoASH and releases NADH and CO2.

Step 5: Succinyl CoA then passes through Succinyl CoA synthase, which removes the CoA group, while adding an O(H) group to the C4 carbon, making Succinate.  GDP and Pi are used, while GTP and CoASH are products.  This reaction is reversible (hence the misleading name “Succinyl CoA synthase”!)

Step 6: Succinate is then dehydrogenated via succinate dehydrogenase (duh) to form fumarate.  H2 is eliminated (one from C2 and one from C3) to form a double bond between the two carbons.  The H2 (and its subsequent electrons) are transfered to Q to make Q2(in the ETC) or FAD to FADH2. This enzyme is the only membrane bound enzyme in the cycle and is also known as Complex II of the electron transport chain and the reaction is reversible.

Step 7: Fumarate is then hydrated into malate. The double bond formed in the last step then gains an OH group and a hydrogen (C2 gets OH C3 gets H, though it doesn’t matter, since the molecule is not chiral and either addition would produce the same product.)  Fumarase catalyzes the reaction and water is consumed; the reaction is reversible.

Cute lil fellaStep 8: Malate is then dehydrogenated such that the OH group becomes a =O group, while NAD+ is reduced to NADH and H+ via malate dehydrogenase.  Oxaloacetate is formed and thus the circle is complete.  The reaction is reversible.

Overall, the TCA cycle produces 4 NADH, 1 FADH2 (or QH2) and 1 GTP.  If we take into account that two pyruvates are formed via glycolysis, the total comes to 8 NADH, 2 FADH2 and 2 GTP.  Granted, this isn’t alot of energy, but the payoff from both of these cycles comes as we enter the electron transport chain, our next topic.

Stay tuned, as this study session crams forward!

The Alchemist Kitten