Ketone Bodies

Ketone bodies serve as alternative fuel for cells

Includes,

-        Acetoacetate

-        3-hydroxybutyrate

-        Acetone

Liver mitochondria can convert Acetyl Co derived from fatty acid oxidation into ketone bodies

So, ketone bodies are formed in the liver and oxidized in skeleton muscles, heart muscles and renal cortex. Brain adapt to use them under starvation condition.

 

Ketogenesis

·      Location – Liver

·      During starvation, glycogen reserves are rapidly depleted, body begins to metabolize fat and protein

·      Liver flooded with fatty acid mobilize from adipose tissue

·      Increase hepatic acetyl CoA

·      The entry of acetyl CoA into citric acid cycle, depends on the availability of oxaloacetic acid for the formation of Citric acid

·      During fast or uncontrolled diabetes OAA is used to synthesize glucose (gluconeogenesis) rather than for TCA cycle

·       Therefore, acetyl CoA is channeled into ketone body formation

 

Factors enhancing ketone body formation

 

·       Prolonged fasting

·       Uncontrolled diabetes mellitus

·       High fat diet

·       Severe exercises

·       Factors that facilitate mobilization of free fatty acids from adipose tissue

Regulation of ketogenesis

·       Substrate level regulation

Release of free fatty acids from adipose tissue directly affects the ketogenesis in liver

·       Hormonal regulation of level of fat oxidation

Activated – in the presence of glucagon

Inhibited – in the presence of insulin

·       Acetyl CoA formed by the oxidation of fats can be completely oxidized in the TCA cycle, if the demand for ATP is high.

Utilization of ketone bodies by peripheral tissues ( ketolysis)

·       Ketone bodies used by extra hepatic tissues including brain

·       Excludes cells lacking mitochondria

·       Liver unable to use ketone bodies as fuel, because it lacks thiophorase to oxidize ketone bodies

·       Ketone bodies soluble in water, therefore taken by blood (from liver)

Clinical significance of ketone bodies

·       Excess ketone bodies in the blood – acetone breath of a person can be detected – fruity smell

·       Accumulation of ketone bodies in blood and urine is known as ketosis

-        Blood ketonemia

-        Urine ketoneuria

·       The acid also altered buffers in the blood (donating H ions) causing acidosis and it also impaired the ability to hemoglobin to bind Oxygen

 

Tests for ketone bodies

·       Rothera’s test

-        Nitroprusside in alkaline medium reacts with ketone group to form purple ring

-        Only acetoacetate and acetone

-        Hydroxybutyrate is negative as it lacks the ketone groups

 

·       Ketone body assay kit

-        Quantitatively determination of total ketone bodies