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Ketone BodiesBy: Sunayna JoshiIVth semeter
Books : U.satynarayan,U .charkrapani
What are ketone bodies?
Ketone bodiesThe compouds namely b-hydroxybutyrate Acetoacetate Acetone
Propeties of ketone bodies• The first two compounds are true
ketones.because these two posses keto group (c=o).
• They are water soluble and energy yielding
And today we will deal with.
• Ketogenesis(synthesis of ketone bodies)
• Utilization of ketone bodies• Overproduction of ketone bodies• Regulation of ketone bodies• Ketogenic and antiketogenic
substance• ketoacidosis
Ketogenesis(synthesis of ketone bodies)Occurance : Liver
Enzyme location: Mitocondrial matrix
Ketogensis deals with the formation of :acetyl coA, pyurvate ,amino acids
Definition
During high rates of fatty acid oxidation, primarily in the liver, large amounts of acetyl-CoA are generated. These exceed the capacity of the TCA cycle, and one result is the synthesis of ketone bodies, or ketogenesis.
Reaction at ketogensis
Two molecules of acetyl CoA condense to form acetoacetyl CoA.
Enzyme – thiolase.
Acetoacetyl CoA reacts with acetyl CoA and water to give 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and CoA.
Enzyme: HMG-CoA synthase
3-Hydroxy-3-methylglutaryl CoA is then cleaved to acetyl CoA and acetoacetate.
Enzyme: HMG-CoA lyase
3-Hydroxybutyrate is formed by the reduction of acetoacetate by 3-hydroxybutyrate dehydrogenase. Acetoacetate also
undergoes a slow, spontaneous decarboxylation to acetone.
Fact:The odor of acetone may be detected in the breath of a person who has a high level of acetoacetate in the blood.
Utilization of ketone bodies
water solubleAcetoacetate and b-hydroxybutyrate
serves as imp source of peripheral tissue such as cardiac muscles,renal muscle
Tissue lack mitochondria cannot utilize ketone bodies
B. Ketone bodies are a major fuel in some tissues
Ketone bodies diffuse from the liver mitochondria into the blood and are transported to peripheral tissues. Ketone bodies are important molecules in energy metabolism. Heart muscle and the renal cortex use acetoacetate in preference to glucose in physiological conditions. The brain adapts to the utilization of acetoacetate during starvation and diabetes.
Metabolism Reactions
•3-Hydroxybutyrate is oxidized to produce acetoacetate as well as NADH for use in oxidative phosphorylation.
3-hydroxybutyrate dehydrogenase
Acetoacetate is activated by the transfer of CoA from succinyl CoA in a reaction catalyzed by a specific CoA transferase. Acetoacetyl CoA is cleaved by thiolase to yield two molecules of acetyl CoA (enter the citric acid cycle). CoA transferase is present in all tissues except liver.
Overproduction of ketone bodies KETONEMIA: Rate of synthesis of ketone body increases the rate of utilization
KETONURIA: Increase in production of ketone body and decrease in the
utilization
And both ketonemia and ketonuria are known as ketosis
Common problem of ketosis :The odor of acetone may be
detected in the breath of a person who has a high level of acetoacetate in the blood.
Impairment of the tissue function, most importantly in the central nervous system
KETOSISThe absence of insulin in diabetes
mellitus liver cannot absorb glucose inhibition of glycolysis activation of gluconeogenesis
deficit of oxaloacetate
activation of fatty acid mobilization by adipose tissue
large amounts of acetyl CoA which can not be utilized in Krebs cycle
large amounts of ketone bodies (moderately strong acids)
severe acidosis (ketosis)
Ketosis is associated with: Starvation Uncontrolled diabetis millitus
Regulation of ketogenisis The hormone glucagon stimulates
ketogenisis and insulin inhibits……................
The increased ratio of these promotes diabetes milletus
Ketogenic and antiketogenic substance Include fatty acid and amino acids
(leucine,tyrosine) are ketogenic
Glucose ,glycerol, glucogenic substance (glycine, serine, glutamate)are antiketogenic inhibits ketogenisis
summary of Formation, utilization, and excretion of ketone bodies.
Diabetic Ketoacidosis
Increase in concentration of ketone bodies cause ketoacidosis (DKA)
Carboxyl group has pka value 4 so ,ketone bodies dissociate in blood and then and release H+ ions.
Treatment Principles of Treatment: Careful replacement of fluid deficits. Correction of acidosis &
hyperglycemia via Insulin administration.
Correction of electrolytes imbalance. Treatment of underlying cause.
Monitoring for complications of treatment.
Administration of insulin
Epidemiology DKA is reported in 2-5% of known type 1
diabetic patients in industrialized countries, while it occurs in 35-40% of such patients in Africa.
DKA at the time of first diagnosis of diabetes mellitus is reported in only 2-3% in western Europe, but is seen in 95% of diabetic children in Sudan. Similar results were reported from other African countries .