1. Glucose enters cells from the tissue fluid by facilitated diffusion using a specific glucose carrier protein. This carrier can be controlled (gated) by hormones such as insulin, so that uptake of glucose can be regulated.
2. The first step is the phosphorylation of glucose to form glucose phosphate, using phosphate from ATP. Glucose phosphate no longer fits the membrane carrier, so it can’t leave the cell. This ensures that pure glucose is kept at a very low concentration inside the cell, so it will always diffuse down its concentration gradient from the tissue fluid into the cell. Glucose phosphate is also the starting material for the synthesis of glycogen.
3. Glucose is phosphorylated again (using another ATP) and split into two triose phosphate (3 carbon) sugars. From now on everything happens twice per original glucose molecule.
4. The triose sugar is changed over several steps to form pyruvate, a 3-carbon compound. In these steps some energy is released to form ATP (the only ATP formed in glycolysis), and a hydrogen atom is also released. This hydrogen atom is very important as it stores energy, which is later used by the respiratory chain to make more ATP. The hydrogen atom is taken up and carried to the respiratory chain by the coenzyme NAD, which becomes reduced in the process.
(oxidised form Õ) NAD + H Õ NADH (← reduced form)
Note: rather than write NADH examiners often simply refer to it as reduced NAD or reduced coenzyme
Pyruvate marks the end of glycolysis, the first stage of respiration. In the presence of oxygen pyruvate enters the mitochondrial matrix to proceed with aerobic respiration, but in the absence of oxygen it is converted into lactate (in animals and bacteria) or ethanol (in plants and fungi). These are both examples of anaerobic respiration.
5. Once pyruvate has entered the inside of the mitochondria (the matrix), it is converted to a compound called acetyl CoA. Since this step is between glycolysis and the Krebs Cycle, it is referred to as the link reaction. In this reaction pyruvate loses a CO2 and a hydrogen to form a 2-carbon acetyl compound, which is temporarily attached to another coenzyme called coenzyme A (or just coA), so the product is called acetyl coA. The CO2 diffuses through the mitochondrial and cell membranes by lipid diffusion, out into the tissue fluid and into the blood, where it is carried to the lungs for removal. The hydrogen is taken up by NAD again.
6. The acetyl CoA then enters the Krebs Cycle. It is one of several cyclic metabolic pathways, and is also known as the citric acid cycle or the tricarboxylic acid cycle. The 2-carbon acetyl is transferred from acetyl coA to a 4-carbon intermediate (oxaloacetate) to form a 6-carbon intermediate (citrate). Citrate is then gradually broken down in several steps to re-form the 4-carbon intermediate (oxaloacetate), producing carbon dioxide and hydrogen in the process. As before, the CO2 diffuses out the cell and the hydrogen is taken up by NAD, or by an alternative hydrogen carrier called FAD. These hydrogens are carried to the inner mitochondrial membrane for the final part of respiration.