What does a biological oxidation reaction look like?
Many of the energy-harvesting reactions of metabolism involve the oxidation of a food molecule&endash;removal of a pair of electrons or a pair of hydrogen atoms (i.e. electrons with their associated protons). These reactions may look somewhat different from the oxidation reactions that are familiar to you from chemistry. Some general types of these reactions are given below.
In each case, electrons are transferred to a carrier molecule&endash;usually NAD+ or FAD. Electrons donated to NAD+ make NADH&endash;a molecule where they are less stable (i.e. higher energy) than if they had been donated to FAD to make FADH2. Some electron donors will not be high-enough energy to donate their electrons to NAD+, so their electrons will be donated to FAD.
In some cases, oxidation reactions involve so much release of energy that they can be coupled to the formation of a high-energy phosphate bond. This occurs in reaction 6 of glycolysis, for example. In other cases, the energy release is not great enough for this, and is released as heat instead. Energy harvesting from these latter reactions comes solely in later stages, in the transfer of electrons from the carrier molecule (NADH or FADH2) to a final electron receptor (oxygen), coupled to the synthesis of ATP. This is the electron transport chain and oxidative phosphorylation, which we'll discuss a little bit later in the course.
Example 1) Oxidation of a saturated hydrocarbon bond to an unsaturated hydrocarbon bond. These electrons are relatively low-energy, so are donated to FAD to make FADH2.
Example 2) Oxidation of an alcohol to an aldehyde or ketone. These electrons are transferred to NAD+ to make NADH.
Example 3) Oxidation of an aldehyde to a carboxylic acid. This involves first the addition of water and then the removal of two hydrogen atoms. Usually only the summary reaction is shown. These electrons are transferred to NAD+ to make NADH. Often enough energy is released in this transfer to allow coupling of this oxidation to the formation of a high-energy phosphate bond.
You know from prior experience in this course that the bond that holds the 3rd phosphate to the 2nd phosphate in ATP is a "high-energy" bond. (So is the bond that holds the 2nd phosphate to the 1st, although this is used less often by cells.) The reason this bond is high-energy is that its hydrolysis produces products that are more stable than the reactants. Acid groups, such as the ones on a phosphate molecule, are most stable if the electrons in them can be "spread around" the molecule. This principle is called resonance stabilization, and you'll encounter it in organic chemistry. When two acids are bonded together, their electrons can't be shared as equally and the negative charges on them repel each other. A bond holding two acids together is thus quite unstable, or high energy. These are called anhydride bonds. If they hold two phosphates together, they're phosphoanhydride bonds. If they hold a phosphate to a carboxylic acid, they're mixed anhydrides.
Alcohols, on the other hand, don't have this electron-spreading effect. So a bond holding an acid (such as a phosphate group) to an alcohol is only interfering with the stability of the acid, not the alcohol. These are called ester bonds, and they're more stable (and thus not as high energy) as anhydride bonds.
1,3-biphosphoglycerate, an intermediate in glycolysis, has both types of phosphate bonds, as shown below.
Another type of high-energy bond is a thioester. Hydrolysis of a thioester yields a sulfhydryl group
(-SH) and an acid group. This type of bond holds more energy than a "regular" ester bond, such as the phosphate ester described above. Hydrolysis of a thioester yields enough energy to allow it to be coupled to the synthesis of ATP from ADP and phosphate (or GTP from GDP and phosphate, as happens in the Citric Acid cycle).
If the carbon to be oxidized is immediately adjacent to a carboxylic acid group, oxidation sometimes occurs together with the release of the adjacent carboxylic acid group as carbon dioxide. This occurs in the conversion of pyruvate to acetyl CoA, as well as in the citric acid cycle (isocitrate to alpha-ketoglutarate, and alpha-ketoglutarate to succinyl CoA). If the oxidation is from a ketone to an acid, this reaction yields enough energy to allow both the transfer of electrons to NAD+ and the formation of a high-energy thioester bond. The actual reaction mechanism is quite complex&endash;a simplified version is shown below.
