Ketone bodies

Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy. They are used as a source of energy in the heart and brain. In the brain, they are a vital source in fasting.

The three ketone bodies are acetoacetate, beta-hydroxybutyrate and acetone, although beta-hydroxybutyrate is not technically a ketone but a carboxylic acid.

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Uses in the heart and brain

Ketone bodies can also be used for energy. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce energy, via the Krebs cycle.

The heart gets much of its energy from ketone bodies, although it also uses fatty acids.

The brain gets its energy from ketone bodies when insufficient glucose is available (e.g., when fasting). In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids), but the brain does not. After the diet has been changed to lower blood glucose for 3 days, the brain gets 30% of its energy from ketone bodies. After 4 days, this goes up to 70% (during the initial stages the brain does not burn ketones, since they are an important substrate for lipid synthesis in the brain). The brain retains some need for glucose, because ketone bodies can be broken down for energy only in the mitochondria, and brain cells' long thin axons are too far from mitochondria.^{[citation needed]}

Production

  Ketone bodies are produced from acetyl-CoA (see ketogenesis) mainly in the mitochondrial matrix of liver cells when carbohydrates are so scarce that energy must be obtained from breaking down fatty acids.

Acetone is formed from spontaneous decarboxylation of acetoacetate. In a corresponding manner, the levels of acetone are much lower than those of the other two types of ketone bodies. And, unlike the other two, acetone cannot be converted back to acetyl-CoA, so it is excreted in the urine and exhaled (it can be exhaled readily because it has a high vapor pressure and thus evaporates easily). The exhalation of acetone is responsible for the characteristic "fruity" odour of the breath of persons in ketotic states.

Ketosis and ketoacidosis

Any production of these compounds is called ketogenesis, and this is necessary in small amounts.

But, when excess ketone bodies accumulate, this abnormal (but not necessarily harmful) state is called ketosis. Ketosis can be quantified by sampling the patient's exhaled air, and testing for acetone by gas chromatography.^[1]

When even larger amounts of ketone bodies accumulate such that the body's pH is lowered to dangerously acidic levels, this state is called ketoacidosis.

Impact upon pH

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, subsequent starvation, and the alcohol-induced impairment of the liver's ability to generate glucose (gluconeogenesis)(see alcoholic ketoacidosis).

See also

• Fatty acid metabolism
• Ketogenesis
• Ketosis

References

1. ^ K. Musa-Veloso, S. S. Likhodii and S. C. Cunnane (2002). "Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals". Am J Clin Nutr 76 (1): 65-70.

• Atkins Nutritionals, Inc. Lipolysis and Ketosis
• emerg/135 at eMedicine - Diabetic Ketoacidosis
• Fat metabolism at unisanet.unisa.edu.au
• NHS Direct Online Health Encyclopaedia, Ketosis
• BioCarta Pathways Formation of Ketone Bodies