The Krebs cycle is a biochemical pathway that is used to generate energy through the oxidation of acetyl-coA. It is also used for the synthesis of NADH and for the production of amino acids. Pyruvate is derived through the glycolysis of glucose, which is a six-carbon compound. It is split into two molecules of pyruvate, which is a three-carbon compound. The next step includes the oxidation of pyruvate into acetyl-coA by the enzyme pyruvate dehydrogenase complex. In this reaction, a molecule of carbon dioxide and a molecule of NADH is generated. The acetyl-coA is a two carbon compound. We next have the acetyl-coA combine with oxaloacetate which is a four carbon compound to form citrate. And then we get we get a six carbon compound molecule (Citrate). This reaction gets catalyzed by the enzyme citrate synthase. The citrate then is isomerized into isocitrate by the enzyme aconitase. The isocitrate is oxidized into alpha ketoglutarate (a five carbon compound) by the enzyme isocitrate dehydrogenase and in this reaction a molecule of NAD is reduced to NADH and a molecule of carbon dioxide is generated. Then we have the alpha ketoglutarate converted to succinyl-coA (a four carbon compound) by the enzyme alphaketoglutarate dehydrogenase and we also have a molecule of NAD reduced to NADH during this reaction as well as the release of a molecule of CO2. The enzyme succinyl-coa synthase converts succinyl-coa into succinate. In this reaction a molecule of GTP is generated. Succinate then is converted into fumrate by the enzyme succinate dehydrogenase. In this reaction a molecule of OH2 is generated which is used for the production of FADH2. Fumrate is then converted into malate by the enzyme fumrase. In the last step, the malate is converted into oxaloacetate by malate dehydrogenase. In this reaction NAD is reduced to NADH. Through each cycle of the Krebs cycle we get 3 NADH, 1 FADH2, 1 GTP, 2 CO2. Since Glucose is split into two pyruvate compounds, for each molecule of glucose we have the cycle run twice and we have a total production of 6 NADH, 2 FADH2, 2 GTP, and 4 Carbon Dioxide. All the NADH and FADH2 are then fed to the electron transport chain in order to generate ATP. The inner mitochondrial membrane contains four sets of enzyme complexes. Electrons travel from the first to the fourth electron complex. In this movement energy is generated. This energy is utilized in pumping hydrogen ions into the intermembrane space from the matrix of the mitochondria. This continuous pumping of hydrogen ions into the intermembrane space causes the generation of a higher concentration of hydrogen ions in the intermembrane space as compared to the matrix of the mitochondria. This generates a positive charge in the intermembrane space and a negative charge in the matrix of the mitochondria. This is called the electrochemical gradient. The hydrogen ions cannot cross against this electrochemical gradient because the inner mitochondrial membrane is non-permeable to ions. With the help of a special transporter known as the enzyme ATP synthase. The ATP synthase transports hydrogen ions into the matrix of the mitochondria and uses the energy generated from the flow of hydrogen ions to phosphorylate adenosine diphosphate into adenosine triphosphate. Going back to the electron transport chain complexes, we also have two additional prosthetic groups called the coenzyme Q as well as cytochrome C. Complex one of the electron transport chain is NADH dehydrogenase complex (It’s a dehydrogenase which removes hydrogen from the reduced form of the nicotinamide adenine dinucleotide and it is called a complex because it also contains flavin mononucleotides and iron sulfur compounds). It is also known as the NADH oxido-reductase (Dehydrogenation is an example of oxidation reduction reaction). The first complex is the L-shaped protein complex which is present in the inner mitochondrial membrane. Complex I receives electrons from NADH and transports it further to the electron transport chain. Complex II is known as succinate dehydrogenase complex (It is going to remove hydrogen from the succinate and oxidize it to fumarate, recalling this is a step from the citric acid cycle. In this reaction the reducing equivalent FADH2 is produced, which is utilized for donation of electrons in the electron transport chain). Complex III is called cytochrome reductase and it is also known as Q-cytochrome C oxidoreductase. Cytochromes are a group of proteins which have heme as their complexes. They also have iron core in which the iron can exist in an oxidized or reduced form depending on the electrons it has. Complex III has three types of cytochromes. Cytochrome B, Cytochrome C1 and Cytochrome C. Complex III accepts electrons from the electron transport chain and then transport it to the cytochrome C. The cytochrome C then transports these electrons to the complex IV (Cytochrome C Oxidase) of the electron transport chain. Complex IV is a heme and copper containing complex and it is responsible for the oxidation of cytochrome C (reduction of O2 to H2O). The redox reactions of Complex IV cause the pumping of two hydrogen ions to the intermembrane space. The ATP synthase enzyme uses the flow of hydrogen ions from higher concentration to the lower concentration to generate energy. This energy is used to phosphorylate adenosine diphosphate to adenosine triphosphate. For every four hydrogen ions, which flow through the ATP synthase, one molecule of ATP is generated. One molecule of NADH causes the movement of ten hydrogen ions from the matrix to the intermembrane space. These hydrogen ions then flow back through the ATP synthase and give rise to 2.5 ATPs. One FADH2 causes the movement of six hydrogen ions to the intermembrane space which when moved back, it gives rise to 1.5 ATPs. We can then calculate that 2 NADH from the conversion of glucose to pyruvate will give us five ATPs. Conversion of pyruvate to acetyl-coA will give five ATPs in the ETC. Six NADH from the Krebs cycle will give us fifteen ATPs. The 2FADH2 from the Krebs cycle will give us Three ATPs. We have a total of twenty ATPs from the Krebs cycle, Seven ATPs from the conversion of glucose to pyruvate in glycolysis. We also get Five ATPs from the conversion of pyruvate to acetyl-coA. We can say that we get 32 ATPs per molecule of glucose, which passes through all these biochemical cycles (In some circumstances we can also end up with as much as 38 ATPs). We also have the lactic acid system which is an anaerobic energy system used for moderate exercise that requires around 85 to 90 percent of maximal exercise effort. After 10 to 15 seconds of exercise, the lactic acid system becomes the main producer of ATP within the body lasting for about 30 seconds and up to upwards of 3 minutes (it all varies by intensity). The lactic acid system works by synthesizing new ATP molecules from glycogen. The reaction is known as glycolysis, and because here it does not involve oxygen, it is called anaerobic glycolysis (this occurs when our muscles are working above their lactate threshold, this is unsustainable, as eventually we will need oxygen). As well as ATP being in our muscles, we also have another substance in our muscles known as phosphocreatine or creatine phosphate. We only have enough ATP in our muscles for about two seconds worth of contractions. Phosphocreatine can split to one molecule of Phosphate and one molecule of Creatine (P+C), as well as also releasing energy itself. That energy is used to produce ATP about every 2 seconds. It works when we are pushing our limits (such as sprinting), and it can be considered anaerobic as well (can work upwards to even 10 seconds and it takes about 2-3 minutes to recover the PC system).
