Ketone bodies

Ketone body or ketone bodies is the collective name for the three compounds, mainly engaged in catabolic metabolic states (ie hunger, reducing diet or low carbohydrate diet ) may be formed and may lead to ketosis. Under ketone bodies are acetoacetate sums (also called acetoacetate ), acetone and β -hydroxybutyrate and 3- hydroxybutyrate together. The latter compound is the most significant of the three.

The ketone bodies are formed in the liver from acetyl- CoA, which is derived from the β - oxidation. They provide a transportable form of acetyl- CoA in our body dar. for recovery of the ketone body but brain and muscles must first change by expressing enzymes that are required for the reconversion of ketone bodies to acetyl -CoA. In times of famine, the ketone bodies contribute a significant portion to produce energy. Thus, it is possible after a certain time the brain, rather than to manage with 40 grams with 120 grams of glucose per day.

Metabolism of ketone bodies

Ketogenesis

The synthesis of ketone bodies occurs from two molecules of activated acetic acid, acetyl -CoA, the normal intermediate product of fatty acid degradation. First, the acetoacetyl- CoA using the acetyl-CoA acetyltransferase is formed which, using a further, acetyl -CoA moiety and the enzyme HMG-CoA synthase, to give the intermediate 3-hydroxy- 3-methyl- glutaryl -CoA (HMG-CoA ) is extended. Finally, the HMG- CoA lyase cleaves the acetoacetate. These three steps are exclusively in the mitochondria of liver instead ( Lynen cycle). 3-hydroxybutyrate finally generated in the cytosol through the D- beta-hydroxybutyrate dehydrogenase.

HMG -CoA is also an end product in the degradation of the amino acid leucine, acetoacetate formed during the degradation of the amino acids phenylalanine and tyrosine.

By spontaneous decarboxylation of acetoacetate formed from acetone; it is sometimes in the breath of diabetics and dieters or even in animals that are suffering from ketosis to perceive. It can not be used by the body. The proportion of acetone to the ketone bodies, however, is low.

Metabolism

From D- β -hydroxybutyrate 3- hydroxybutyrate dehydrogenase acetoacetate can be obtained by means of the enzyme; the reaction is easily reversible. The 3- ketoacid CoA - transferase transfers CoA to acetoacetate, while succinate is released. Ultimately derived from acetoacetyl- CoA and acetyl-CoA CoA twice; catalyzing this reaction concerned the acetyl -CoA acetyltransferase, also the reverse of a taking place in the synthesis reaction.

This activation takes place of the ketone bodies into the mitochondrial matrix of all the cells that can process the ketone bodies but not in the liver. Finally, the thus obtained acetyl -CoA feeds into the citric acid cycle, where it gained by oxidation energy.

Ketone bodies and diabetes

In type 1 diabetes mellitus (diabetes) is found in absolute insulin deficiency increased ketone bodies in the urine ( ketonuria ). This is due to a too high concentration of the same in the blood. As glucose separates the kidney from the ketone bodies at an elevated blood concentration.

Reason for the increased production of ketone bodies is the lack of insulin: Although actually is enough glucose in the blood, it can not be transported into the cells without the siren insulin. Therefore, despite elevated blood glucose levels in the blood is produced in the cells of a glucose deficiency. This leads to the breakdown of fat (lipolysis ) for energy. While insulin stimulates the development of depot fat, insulin deficiency promotes lipolysis. A low insulin levels induced lipolysis is typical of the hunger metabolism. Ketone bodies are formed when the degradation product of the fatty acids, acetyl -CoA, due to low Oxalacetatkonzentration can not enter the citric acid cycle. Oxaloacetate can be synthesized in an anaplerotic reaction of pyruvate. Pyruvate is the end product of glycolysis. Which in the case of diabetes mellitus present in the cells low glucose levels resulting in low amounts of pyruvate, and thus low amounts of oxaloacetate, which favors the formation of ketone bodies from acetyl -CoA. Too many ketone bodies in the blood whose pH is lowered and there is a ketoacidosis, which results in the worst case to a ketoacidotic coma. Therefore, only type 1 is relevant in diabetes mellitus type 2, the body has formed a resistance to insulin. The insulin levels in the blood is thus high.

A typical symptom of ketoacidosis is the smell of acetone (nail polish remover ) in the breath as the ketone bodies are exhaled through this.

In case of persistent hypoglycemia with simultaneously decreased Ketokörperzahl in the blood, however, must be considered in the presence of a fatty acid oxidation disorder. Example is a medium - chain acyl-CoA dehydrogenase deficiency.