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  • Laboratory Medicine - Ketone Bodies

    Загружено:

    Edward Winchesterr
    33 просмотров13 страниц
    Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2] or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. The latter cannot be obtained from the blood, because they cannot pass through the blood–brain barrier. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted. (These glycogen stores are depleted after only 24 hours of fasting.)[1] When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted back into acetyl-CoA except via detoxification in the liver where it is converted into lactic acid, which can, in turn, be oxidized into pyruvic acid, and only then into acetyl-CoA. Ketone bodies have a characteristic smell, which can easily be detected in the breath of persons in ketosis and ketoacidosis. It is often described as fruity or like nail polish remover (which usually contains acetone or ethyl acetate). Apart from the three endogenous ketone bodies, acetone, acetoacetic acid, and beta-hydroxybutyric acid,[4] other ketone bodies like beta-ketopentanoate and beta-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides, such as triheptanoin.

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    Laboratory Medicine -- Ketone Bodies

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    Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2] or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. The latter cannot be obtained from the blood, because they cannot pass through the blood–brain barrier. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted. (These glycogen stores are depleted after only 24 hours of fasting.)[1] When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted back into acetyl-CoA except via detoxification in the liver where it is converted into lactic acid, which can, in turn, be oxidized into pyruvic acid, and only then into acetyl-CoA. Ketone bodies have a characteristic smell, which can easily be detected in the breath of persons in ketosis and ketoacidosis. It is often described as fruity or like nail polish remover (which usually contains acetone or ethyl acetate). Apart from the three endogenous ketone bodies, acetone, acetoacetic acid, and beta-hydroxybutyric acid,[4] other ketone bodies like beta-ketopentanoate and beta-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides, such as triheptanoin.

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    33 просмотров13 страниц

    Laboratory Medicine - Ketone Bodies

    Загружено:

    Edward Winchesterr
    Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2] or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. The latter cannot be obtained from the blood, because they cannot pass through the blood–brain barrier. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted. (These glycogen stores are depleted after only 24 hours of fasting.)[1] When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted back into acetyl-CoA except via detoxification in the liver where it is converted into lactic acid, which can, in turn, be oxidized into pyruvic acid, and only then into acetyl-CoA. Ketone bodies have a characteristic smell, which can easily be detected in the breath of persons in ketosis and ketoacidosis. It is often described as fruity or like nail polish remover (which usually contains acetone or ethyl acetate). Apart from the three endogenous ketone bodies, acetone, acetoacetic acid, and beta-hydroxybutyric acid,[4] other ketone bodies like beta-ketopentanoate and beta-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides, such as triheptanoin.

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    Ketone Bodies

    Metabolism of Ketone Bodies


    It includes:
    1.Ketogenesis , synthesis of ketone bodies in liver
    mitochondria .
    2.

    Ketolysis,

    oxidation

    of

    ketone

    mitochondria of extrahepatic tissues..

    bodies

    in

    Ketone bodies are weak organic acids,


    include:
    Acetoacetate
    -hydroxybutyrate
    Acetone

    Ketogenesis
    Site:
    occurs in mitochondria of liver cells due to presence of two
    Key enzymes:
    HMG-CoA synthase
    HMG-CoAlyase
    Synthesis of ketone bodies
    Occurs only inside hepatic mitochondria, Ketone bodies are
    formed in liver cells, from active acetate derived mainly
    from oxidation of fatty acids and ketogenic amino acids.

    Ketogenesis

    Synthesis of ketone bodies


    Acetyl CoA + acetyl CoA

    acetoacetyl CoA

    thiolase

    Acetoacetyl CoA + acetyl CoA

    HMGCoA

    HMGCoA + CoASH

    synthase

    HMGCoA

    HMGCoA

    lyase

    Acetoacetate + acetylCoA

    Acetoacetate can undergo spontaneous decarboxylation to


    acetone, or be enzymatically converted to -hydroxybutyrate
    through the action of -hydroxybutyrate dehydrogenase

    Regulation Of Ketogenesis
    A. Factors increase Ketogenesis:
    All factors which increase rate of lipolysis, increase release FFA
    from tissues to liver and increase rate of ketgenesis
    1. Fasting and starvation
    2. Carbohydrate deficiency
    3. High fat diet
    4. Hyper-secretion of anti-insulin hormone (glucagone )
    5. Diabetes mellitus due to impaired glucose oxidation and
    increased fatty acid oxidation, leading to over production of
    acetyl-CoA and increased synthesis of ketone bodies.

    B. Factors decrease Ketogenesis:


    1. Feeding of glucose or carbohydrate
    2. Treatment with insulin.
    Important of Ketone Bodies
    1.Ketogenesis supplies ketone bodies to extra-hepatic tissues such
    as heart and skeletal muscle where they are oxidized easier
    than oxidation of fatty acid.
    2. Also brain tissues accommodate for oxidation ketone bodies in
    long starvation (5day) but never oxidize fatty acid.
    3. Some ketone bodies (Acetoacetate and -hydroxybutyrate,)
    serve as major substrates for the biosynthesis of neonatal
    cerebral lipids.

    KETOLYSIS :
    Means oxidation of ketone bodies.
    Site:
    Ketolysis occurs in the mitochondria of extra-hepatic
    tissues (Muscle, Heart - BrainKidney ) due to
    presence of ketoacyl-CoA- transferase
    or
    acetoacetate:succinyl-CoA transferase, (Key enzyme
    of ketolysis).
    B hydroxybutyrate converted to acetoacetate ( by
    reversal 3- hydroxybutyrate dehydrogenase). Then
    acetoacetate is converted to active acetate as follow.

    Ketolysis

    Important of ketolysis:
    It is the main source of energy in extrahepatic
    tissues

    during

    fasting,

    carbohydrates deficiency.

    starvation

    and

    Ketosis

    Ketosis is a condition characterized by elevated levels of


    ketone bodies in blood
    (Ketoacidosis )and their
    excretion in urine (Ketonuria).

    Ketone bodies are organic acids so in Ketoacidosis ,


    characterized by elevation ketone bodies in the blood
    and patients suffer from acidosis lower pH of blood (less
    than 7.3). The acidosis condition in patients is dangerous
    condition , if not treated can led to coma or even death.

    Causes of ketosis or ketoacidosis:


    all causes increase ketogenesis such as
    1. Fasting and starvation
    2. High fat diet with Carbohydrate deficiency
    3. Hypersecrestion of anti-insulin hormone such as
    glucagone and epinephrine hormones.
    4. Diabetes mellitus due to impaired glucose oxidation
    and increased fatty acid oxidation.

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