Ketone bodies

Ketone bodies are certain chemicals produced mainly in the liver; they provide much of the energy to heart tissue and during starvation also to the brain. In diabetes, ketone bodies can accumulate in the blood, causing diabetic ketoacidosis, a dangerous condition.

The chemicals acetoacetate, acetone and beta-hydroxybutyrate[?] are collectively known as ketone bodies; note that the first two are ketones while the third is not.

Ketone bodies are formed in the mitochondria of liver cells from acetyl-Coenzyme A (Acetyl-CoA). Acetyl-CoA results from the breakdown of carbohydrates, lipids and amino acids. Normally, the acetyl group of acetyl-CoA enters the citric acid cycle to generate energy in the form of ATP. Some of it can also leave the mitochondria in the form of citrate to participate in the synthesis of fatty acids. A third possible fate of acetyl-CoA is the production of ketone bodies; this happens if acetyl-CoA levels are high and the citric acid cycle cannot keep up. The creation of ketone bodies is also known as ketogenesis.

Ketone bodies are transported from the liver through the blood to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce energy. The heart derives most of its energy in this way. Most other tissues obtain most of their energy from fatty acid breakdown. An important exception is the brain, which obtains its energy from glucose. If glucose levels are low, such as during starvation, the brain uses ketone bodies as energy source instead.

The levels of acetone are much lower than those of the other two types of ketone bodies. It cannot be converted back to acetyl-CoA and is exreted with urine and breathed out.

Both acetoacetate and beta-hydroxybutyrate are acidic, and if levels of ketone bodies are too high, the pH of the blood falls, resulting in a condition known as ketoacidosis. This happens in untreated diabetes (see diabetic ketoacidosis) and also in alcoholics after binge drinking and subsequent starvation (see alcoholic ketoacidosis[?]).

The ultimate reason for ketoacidosis in these cases is the same: the cell does not have enough glucose (in the case of diabetes because lack of insulin prevents the cell from taking up glucose, in the case of fasting because there is no glucose around). This means that acetyl-CoA is mainly produced from the breakdown of fatty acids and fed into the citric acid cycle. The intermediates of the citric acid cycle are used for other anabolic purposes as well and have to be replenished. Normally, this is done by converting pyruvate into oxaloacetate[?] or L-malatate[?] (the so-called anaplerotic pathways). But pyruvate is the end product of glycolysis, the breakdown of glucose, and glucose is not present in the case we consider. This means that the citric acid cycle intermediates cannot be replenished, the cycle slows down, acetyl-CoA accumulates and ketogenesis becomes more important.