The first stage oxidative respiration is a single oxidative reaction in which one of the three carbons of pyruvate is cleaved off, departing as CO2 (chemists call a reaction of this kind a decarboxylation) and leaving behind two remnants: (1) a pair of electrons and their associated hydrogen, which reduce NAD+ to NADH; and (2) a two-carbon fragment called acetyel group. This reaction is complex, involving three intermediate stages, and is catalyzed within mitochondria by an assembly of enzymes, a multi-enzyme complex. The complex of enzymes that removes the CO2 from pyruvate, called pyruvate dehydrogenase, is one of the largest enzymes known - it contains some 72 subunits! In the course of the reaction, the two-carbon acetyl fragment removed from pyruvate is added to a cofactor, a carrier molecule called coenzyme A, forming a compound called acetyl-CoA: Pyruvate + NAD+ + CoA ---> Acetyl CoA + NADH + CO2.
Stage A: Three priming reactions (reactions 1 to 3) set the scene. In the first reaction, acetyl-CoA joins the cycle, and then chemical groups are rearranged. Stage B: It is in the second stage (reactions 4 to 9) that energy extraction occurs. Four of the six reactions are oxidations in which electrons are removed, and one generates an ATP equivalent directly by substrate-level phosphorylation.
The extracted electrons are temporarily housed within NADH molecules. In one reaction, the extracted electrons are not energetic enough to reduce NAD +, and a different coenzyme, flavin adenine dinucleodite (FAD), is used to carry these less energetic electrons, and is reduced to FADH2.
The NADH molecules carry their electrons to the cell membrane (the FADH2 is already attached to it) and there transfer them to a complex membrane-embedded protein called NADH dehydrogenase. The electrons are then passed on to a series of cytochromes and other carrier molecules, one fatter the other, losing much of their energy in the process by driving several transmembrane proton pumps. This series of membrane-associated electron carriers is collectively called the electron transport chain. At the terminal step of the electron transport chain, the electrons are passed to the cytochrome c oxidase complex, which uses four of the electrons to reduce a molecule of oxygen gas and form water: O2 + 4H+ + 4e- --> 2H2O. The electrons transport chain puts the electrons garnered from the oxidation of glucose to work driving proton-pumping channels . The ultimate accept of the electrons harvested from pyruvate is oxygen gas, which is reduced to form water. The internal compartment or matrix of a mitochonrdion contains the enzymes that carry out the reactions of the citric acid cycle. Electrons harvested there by the oxidative respiration are used (via energy chains along the electron transport chain) to pump protons out of the matrix into the outer compartment, sometimes called the inter-membrane space. The electrons harvested from glucose and carried to the membrane by NADH drive protons out across membranes. The return of the protons into the mitochrondrion by diffusion generates ATP.
Oxidative respiration is 18 times more efficient than glycolysis at converting the chemical energy of glucose into ATP. It produces 36 molecules of ATP from each glucose molecule consumed, compared with the two that are produce by glycolysis.
Like nibbling down the end of a candy cane, the long fatty acid chain (which might typically have 16 or more CH2 links) is progressively shortened, until the entire fatty acid is converted to acetyl-CoA. This process is known as beta-oxidation. The regulation of these biochemical pathways by levels of ATP is an example of feedback inhibition.
