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 .