Ketone bodies

From Academic Kids

Ketone bodies are certain chemicals produced mainly in the liver when fatty acids are broken down for energy. They provide much of the energy to heart tissue and during starvation also to the brain. In Type 1 diabetes, excessive ketone bodies can accumulate in the blood, causing diabetic ketoacidosis, a dangerous condition.

The three chemicals known as ketone bodies are acetoacetate, acetone and beta-hydroxybutyrate; 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.

Most tissues obtain the bulk of their energy from glucose, but when there's no glucose, they can use ketone bodies for energy. 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 much of its energy in this way, although it also uses a lot of fatty acids.

Ketone bodies are particularly important for the brain, because if glucose levels are low, as in starvation, the brain can only use ketone bodies as its energy source (most other tissues have additional backup energy sources besides ketone bodies). After a 3-day fast, the brain gets 30% of the energy from ketone bodies. After 40 days, this goes up to 70%. (During the initial stages of starvation the brain does not burn ketones, since they are an important substrate for lipid synthesis in the brain.) The brain retains a residual need for glucose, because ketone bodies can only provide energy aerobically (with oxygen) via mitochondria. In the neuron's long thin axons, much of the active cellular membrane is too far from the nearest mitochondria, so it must derive its energy from glucose anerobically (without oxygen).[1] (

Acetone is formed from spontaneous decarboxylation of acetoacetate. Correspondingly, 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, so it is excreted in the urine and exhaled (it can be exhaled because it has a high vapor pressure and thus evaporates easily). The exhalation of acetone is responsible for the characteristic "fruity" odor of the breath of persons in ketotic states.

Both acetoacetate and beta-hydroxybutyrate are acidic, and if levels of these ketone bodies are too high, the pH of the blood drops, resulting in ketoacidosis. This happens in untreated Type I diabetes (see diabetic ketoacidosis) and also in alcoholics after binge drinking and subsequent starvation (see alcoholic ketoacidosis).

The ultimate reason for ketoacidosis in both 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 starvation because there is less glucose around). Therefore, 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-malate (the anaplerotic reactions). But pyruvate is the end product of glycolysis, the breakdown of glucose, and glucose levels are lower in the cases 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.


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