Metabolism of Lipids 9 Sections27 LessonsLifetime
Ketone Bodies Metabolism
The primary source of energy for brain is glucose.
When glucose level is DECREASED the brain switches to the secondary source of fuel i.e. ketone bodies.
Muscles can also use ketone bodies as a fuel when there is decreased glucose and increased β-Oxidation of Fatty acids.
In the conditions of decreased glucose the body switches to the 2nd source of fuel i.e. Fatty acid oxidation.
There is only ONE organ in the body that makes Ketone bodies and that is LIVER.
Ketone bodies are synthesized in the liver mitochondria.
When Fatty acids are mobilized from the adipose tissue, they are poured into the body tissues like muscles.
When Fatty acids reach liver they are activated to Fatty Acyl-CoA and enter the Ketone Bodies synthesis pathway.
Reasons for ↑ Ketone bodies formation
- Low Blood Glucose level.
- Prolonged Starvation.
- Uncontrolled DM (Type I).
- Keto diet.
Synthesis of Ketone Bodies
In starvation, when fatty acids reach the liver they are activated to Fatty Acyl CoA and enter the Ketone bodies synthesis pathway.
There is no hormonal control over that.
How does the liver know when to make ketone bodies when you are starving?
From β-Oxidation when Acetyl CoA is formed it goes into the Krebs’ cycle in normal conditions to make ATP.
But in starvation Acetyl CoA does not enter the Krebs’ cycle.
Instead enters ketone body synthesis pathway.
Steps of Ketone bodies Synthesis
When Acetyl CoA is formed in β-Oxidation , it enters the ketone bodies synthesis pathway when the person is in starvation.
Two Acetyl CoA (2C) join to form Acetoacetyl CoA (4C).
In the next step one more Acetyl CoA is added to form HMG-CoA (6C).
Enzyme is HMG-CoA synthase.
Then, in the next step, HMG-CoA lyase acts on it to form Acetoacetate (1st Ketone body).
Acetoacetate is then converted into 3-Hydroxybutyrate also known as β-hydroxybutyrate (2nd Ketone body).
Enzyme in this step is 3-Hydroxybutyrate. In this step one NADH is converted to NAD+.
Acetoacetate is also acted upon by Acetoacetate Decarboxylase to form Acetone (3rd Ketone body).
This reaction is spontaneous and CO2 is released in this step.
- This HMG-CoA in KB synthesis is different from that of Cholesterol synthesis (location).
- This HMG-CoA is present in liver mitochondria only while,
- HMG-CoA in cholesterol synthesis is present in every cell of the body (in ER) except erythrocytes.
- They NEVER mix.
- Acetone is useless as fuel, but it is diagnostic in conditions like starvation and Diabetic ketoacidosis.
- Why Acetyl CoA does not go into the Krebs’ cycle during starvation?
- Acetyl CoA does not go into the Krebs’ cycle as it need Oxaloacetate (OAA) to form Citrate.
- In starvation, OAA goes out of the mitochondria into the cytoplasm for Gluconeogenesis.
- As OAA is not available so Acetyl CoA goes to form ketone bodies.
Next steps of metabolism
After synthesis, the ketone bodies go into the blood.
Acetone cannot be used as fuel – only diagnostic.
The other two ketone bodies go to the extrahepatic cells and into the mitochondria of extrahepatic cells.
In the mitochondria of extrahepatic cells β-hydroxybutyrate is converted back to acetoacetate.
One NADH is formed (2.5 ATP).
Acetoacetate is then activated by the enzyme Thiophorase which is absent in liver to form Acetoacetyl CoA.
Acetoacetyl CoA is then cleaved to form 2 acetyl CoA.
Each acetyl CoA condenses with OAA to form citrate.
Citrate enters in the Krebs’ cycle to generate ATP.
Each Acetyl CoA generates 10 ATP. So, a total of 20 ATP + 2 GTP are generated from each of the ketone bodies.
- Oxaloacetate (OAA) is not present in liver then why it is present in extrahepatic tissue?
- REASON – Location.
- Extrahepatic tissues do not make glucose so there is plenty of OAA present in extrahepatic cells.
When does liver start making ketone bodies?
Liver starts making ketone bodies 90 minutes after eating a high carbohydrate meal and these ketone bodies are dumped into the blood.
These cannot be measured because as soon as they come in the blood muscles and renal cortex use them.
In prolonged starvation the ketone bodies synthesis pathway becomes the major pathway.
Brain also adapts to using ketone bodies in prolonged starvation and spares glucose for erythrocytes.
Ketone bodies form after eating high carbohydrate meal?????
PLZ READ CAREFULLY. KETONE BODIES ARE FORMED WHEN THE GLUCOSE LEVEL IS DECREASED AS IN STARVATION.
WRITTEN IN THE SECOND LINE OF LESSON.
ANYWAY I HAVE HIGHLIGHTED IT NOW.