The Krebs cycle was identified in 1937 by Hans Krebs and is the key metabolic pathway that connects carbohydrate, fat and protein metabolism. An appreciation of this process is essential to understanding how the cells of the human body actually utilise the substances that are produced from our food as a result of digestion, and also how we have evolved over millions of years to utilise alternative energy sources besides glucose. And a grasp of this latter concept is absolutely vital in understanding the most efficient way to tackle obesity.
The cycle involves a number of chemical reactions whereby molecules are converted to other molecules by 8 different enzymes that completely oxidize acetate, in the form of acetyl-CoA, into two molecules each of carbon dioxide and water. The really good thing however is that you are not required to know the names nor chemical formulae of these different molecules – merely an understanding will suffice.
In the process of the cycle, energy is generated by oxidative phosphorylation and this energy is then used to power the cellular processes that are occurring constantly in our body. Whilst glucose is the primary substrate for the Krebs cycle there are also a number of steps that allow fatty acids which are the breakdown products of triglycerides, and amino acids which are the breakdown products of proteins, to enter the cycle thereby allowing both of these macronutrients to be used as body fuel.
As you will have seen from the presentation on fat metabolism, fatty acids are provided by the breakdown of triglycerides in our food but also from stored body fat. The latter process is called lipolysis. Not only does it release fatty acids but it also produces glycerol which itself can enter the glycolytic pathway which converts glucose into pyruvate. The latter compound is then oxidised to become acetyl-CoA which then leads into the Krebs cycle. Fatty acids themselves are converted to acetyl-CoA and enter the Krebs cycle via this route.
Glycolysis as previous mentioned is the conversion of glucose to pyruvate via a molecule called glucose 6-phosphate. Fructose, which in addition to glucose is the other important component of sucrose or table sugar, is similarly phosphorylated to fructose 6-phosphate and can enter the glycolysis pathway in this form. It is for this reason that the intake of fructose which is found in abundance in fruit, needs to be limited such that the glycolysis pathway is effectively shut down, in order to favour the lipolysis pathway, thereby promoting loss of adipose tissue and hence promoting weight loss.
As seen in the presentation entitled gluconeogenesis, this pathway describes how protein both ingested and stored, in the form of muscle, is used to maintain blood glucose at its minimum level during periods of fasting. This is obviously essential as there are some cells, in particular those within the central nervous system, that have an obligation to utilise glucose as its energy source. However, as previously discussed in the presentation entitled Ketone Bodies, the central nervous system can switch to using these compounds as its energy source after approximately 3-4 days of fasting. The ketone bodies -acetoacetate and beta-hydroxybutyrate - enter the Krebs cycle via conversion to aceto-acetyl-CoA and which then produces two molecules of acetyl-CoA thereby gaining entry in this fashion. Several amino acids can enter the Krebs cycle at various steps, by having the amino group removed. This makes ammonia as a waste molecule which is then converted to urea and this is then removed from the body in the urine.