Ketone Bodies

Atif Hassan Khirelsied, B.Sc., M.Sc., Ph.D.

Department of Biochemistry

Faculty of Medicine and Health Sciences

International University of Africa, Khartoum, Sudan

Ketone bodies

• Ketone bodies (KBs)  are two molecules, acetoacetateand β‐hydroxybutyrate.

• KBs are water soluble and can be transported in the blood to all tissues including the brain.blood to all tissues  including the brain.

KB th i ll d ll diti b t• KBs synthesis occurs normally under all conditions, but increases during starvation or lack of insulin.

Ketone bodies are synthesized in the liver and utilized by extrahepatic tissuesextrahepatic tissues

Ketone bodies synthesis increases with prolonged  fastingfasting

Ketone bodies synthesis (ketogenesis)synthesis (ketogenesis)

Ketone bodies synthesis (ketogenesis)

Acetoacetate may further be reduced to β hydroxybutyrateAcetoacetate may further be reduced to β‐hydroxybutyrate, or spontaneously  decarboxylated to acetone.

The regulation of Ketone bodies synthesis

The regulation of Ketone bodies synthesis

1. The supply of fatty acids is increased.

2. The malonyl CoA inhibition of CPTI is lifted by inactivation of acetyl CoA carboxylaseacetyl CoA carboxylase.

3. Increased β‐oxidation increases NADH and FAD(2H). β ( )

4. Oxaloacetate is converted into malate because of the high NADH levels, and the malate enters the cytoplasm for gluconeogenesis. 

5. Acetyl CoA is diverted from the TCA cycle into ketogenesisbecause of low oxaloacetate levelsbecause of low oxaloacetate levels.

Ketone bodies utilization (ketolysis)

• Ketone bodies can be utilized by all aerobic tissues h liexcept the liver.

Th d d d i t t l C A hi h lti t l• They are degraded into acetyl‐CoA which ultimately enters the TCA cycle.

• The liver has little β‐ketoacyl‐CoA transferase, and therefore little ability to convert acetoacetate intotherefore little ability to convert acetoacetate into acetyl‐CoA.

• Lack of this enzyme in the liver prevents the futile cycle.cycle.

Ketone bodies utilization

Ketosis

Ketosis occurs in:Di b lli• Diabetes mellitus 

• High fat dietsP l d f ti ( t ti )• Prolonged fasting (starvation).

Th b i d t t t ti b i i k t• The brain adapts to starvation by increasing ketonebodies utilization.

• Ketone bodies accumulation in blood lowers blood pH below 7 4 (acidosis)below 7.4 (acidosis).