Ketone bodies

Ketone bodies

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

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

Uses in the heart and brain

Ketone bodies can 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 little energy from ketone bodies, it uses mainly 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). In time the brain reduces its glucose requirements from 120g to 40g per day.

Production

Ketone bodies are produced from acetyl-CoA (see ketogenesis) mainly in the mitochondrial matrix of hepatocytes 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. [cite journal | author = K. Musa-Veloso, S. S. Likhodii and S. C. Cunnane | title = Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals | year = 2002 | journal = Am J Clin Nutr | volume = 76 | issue = 1 | pages = 65–70 | doi = | url = http://www.ajcn.org/cgi/content/abstract/76/1/65 | pmid = 12081817 ] Many diabetics self test for the presence of ketones using blood or urine testing kits.

When even larger amounts of ketone bodies accumulate such that the blood'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
* Ketones (General article. Not limited to the three ketones occurring in the body).

References

External links

* Atkins Nutritionals, Inc. [http://atkins.com/helpatkins/newfaq/categories/LipolysisKetosis.html Lipolysis and Ketosis]
* - Diabetic Ketoacidosis
* [http://www.unisanet.unisa.edu.au/08366/h&p2fat.htm Fat metabolism at unisanet.unisa.edu.au]
* NHS Direct Online Health Encyclopaedia, [http://www.nhsdirect.nhs.uk/en.asp?TopicID=274 Ketosis]
* BioCarta Pathways [http://www.biocarta.com/pathfiles/ketonebodiesPathway.asp Formation of Ketone Bodies]
*


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