Hello again my Biochemistry enthusiasts! 🙂 This is Reshi here, and boy has it been a stressful semester so far. To add to the stress, I wasn’t sure what I was supposed to write for this topic of TCA and ETC. Well, I remember the ETC part from high school, but when I saw TCA, I got a mental block. I don’t remember ever hearing about that cycle! I probably must have fallen asleep in my Biology class again. So on doing some research, I saw that the TCA cycle is the same thing as the citric acid cycle, or the Krebs cycle. Now that I remember lol.
Since we are on topic of the TCA (tricarboxylic acid) cycle, or Krebs cycle as I remember it, I would like to share a few thoughts on it, as well as on the ETC (electron transport chain). So we are all familiar with the fact that cellular respiration is essential for us to produce energy. The site of energy formation is the mitochondria and thus, these structures are plentiful in our body cells. As Richie had discussed in last week’s post, glycolysis is the first step in this energy formation process. The whole point of glycolysis, well at least in my opinion, is to produce two molecules of pyruvate, as well as two molecules each of adenosine triphosphate (ATP) and NADH. A link reaction then occurs in the mitochondrial matrix, which links the glycolysis and Krebs cycle together. Here, the pyruvate molecules become oxidized to form Acetyl CoA. 2 pyruvate + CoA + 2NAD+ —> 2 Acetyl CoA + 2CO2 + 2NADH
Now this is where my part comes in. The formation of the product Acetyl CoA is a vital step because it is used in the initial step of the TCA cycle. Before I go further, it is important to note that while glycolysis occurs in the cytoplasm of cells, the TCA cycle takes place in the matrix of mitochondria. This is where things can get pretty technical, so just bear with me as I try to simplify this process. So we have our two molecules of Acetyl CoA that have been formed essentially from one glucose molecule. However, only one of these 2-carbon structures can undergo the TCA cycle at a time, and thus, the cycle must be repeated so that both Acetyl CoA molecules are utilized.
- At the beginning of the cycle, Acetyl CoA interacts with a 4-carbon structure known as oxaloacetate to form citrate, which is a 6-carbon compound. This reaction is catalyzed by citrate synthase. It is important that side reactions be kept to a minimum, since this initial step is very crucial to the entire cycle.
- Since the position of one of the hydroxyl groups on the citrate molecule is not conducive to the process of oxidative decarboxylation (an oxidation reaction whereby a Carbon atom is lost), the structure needs to be slightly rearranged (Berg, Stryer, and Tymoczko 2002). Hence, the isomerization of citrate to isocitrate occurs. Isocitrate is also a 6-carbon molecule.
- The next step is the conversion of isocitrate to α-ketoglutarate. We are moving from a 6-carbon to a 5-carbon structure, which indicates that oxidative decarboxylation is taking place. This redox reaction is catalyzed by isocitrate dehydrogenase. NAD+, an electron carrier, becomes reduced to NADH by utilizing the energy released from converting isocitrate to α-ketoglutarate.
- Another oxidative decarboxylation reaction occurs in order for α-ketoglutarate to be converted to succinyl CoA, which is a 4-carbon molecule. Again, NAD+ is reduced to NADH and H+.
- Succinyl CoA then goes on to form succinate, and is catalyzed by succinyl CoA synthetase. Guanosine Diphosphate (GDP) uses the energy given off from this reaction to combine with an inorganic phosphate and forms Guanosine Triphosphate (GTP). In the presence of nucleoside diphosphate kinase, GTP can be easily converted to ATP. (GDP—>GTP—>ATP) 🙂
- The last set of reactions is the conversion of succinate to the product oxaloacetate. However, this conversion has a few steps in between. Firstly, the succinate undergoes an oxidation reaction catalyzed by succinate dehydrogenase to produce fumarate. Another electron carrier, FAD, is involved in this particular reaction instead of NAD. This is because FAD is capable of removing two hydrogen atoms from a given molecule. The FAD undergoes a reduction reaction to form FADH2. Then, a hydrolysis reaction occurs in the presence of fumarase catalyst, whereby fumarate is converted to malate. Lastly, malate undergoes oxidation with the catalyst malate dehydrogenase to form oxaloacetate. This time, NAD is used as the electron carrier and becomes reduced to NADH+ and H+.
So basically, after that long, complicated process, the whole point of the Krebs cycle is to generate reduced NAD and Reduced FAD so that they can be used in the next step of cellular respiration, which is the Electron Transport Chain (ETC). In the ETC, a series of redox reactions occur as the electrons pass along the electron carriers. These carriers (large protein complexes) release energy, and this energy is used to make ATP. This process can be summed up in the Chemiosmostic Theory. I think I should expand a little more on this very interesting hypothesis.
The reduced NAD molecules go into the ETC and loses their Hydrogen. Each Hydrogen atom that has been given up splits into its constituent protons and electrons.
H —>H+ + e–
The protons that arise from the split Hydrogen atoms are pumped into the intermembranal space in the mitochondria to increase the proton concentration. Since there is a high concentration of positive protons in the intermembranal space, these protons will move from a higher concentration to a lower concentration in the mitochondrial matrix down its electrochemical gradient. As protons leak from the intermembranal space through special protein complexes back into the matrix, the energy dissipated is used by ATP synthase to convert one ADP (adenosine diphosphate) to one ATP (adenosine triphosphate) for each pair of protons. Thus, each reduced NAD pumped three pairs of protons to produce three ATP molecules. Likewise, each reduced FAD pumps two pairs of proton which produces two ATP. At the end of the ETC, the electrons combine with a Hydrogen ion and an Oxygen atom to form water.
½ O2 + 2H+ + 2e– —>H2O
The formation of water results from the electron carrier cytochrome c which contains the large transmembranal protein, cytochrome oxidase, to catalyze the above reaction while facilitating the pumping of protons from the matrix into the intermembranal space via energy released from the electron produced from the first equation. Okay, I know that was a lot of information to take in, but take it one step at a time. Just remember that respiration is not simply the intake and exhalation of air, but a series of biochemical reactions that result in the formation of energy. Sadly this is my last reflection 😦 and I must say, I really enjoyed doing these posts! So until we meet again in the future, this is Reshi closing off. Keep calm and study hard my Biocheminions!!!! 🙂
Link reaction and Krebs- http://img.docstoccdn.com/thumb/orig/44745072.png.
Cellular respiration- http://www.uic.edu/classes/bios/bios100/lectures/09_08_cellular_respiratio-L.jpg
Link reaction- http://revisionworld.co.uk/files/LinkReaction.JPG.