6. ▣ Under normal fed state:
The hepatic production of acetoacetate and
β hydroxybutyrate is minimal and the
concentration of these compounds in the
blood is very low (does not exceed 1 mg%
or <0.2 mmol/L).
.
7. Two molecules of acetyl-CoA are condensed to
form acetoacetyl-CoA.
8. Condensation of acetoacetyl CoA with
acetyl CoA to form HMG CoA
(3 or β hydroxyl- 3or β methyl glutaryl CoA)
catalyzed by HMG CoA synthetase,
9. HMG-CoA lyase enzyme catalyzes the
cleavage of HMG-CoA to acetoacetate and
acetyl CoA.
14. Both acetoacetate and β-hydroxybutyrate can
be transported across the mitochondrial
membrane and the plasma membrane of the
liver cells
enter to the blood stream to be used as a fuel
by other cells of the body.
15. ▣ Acetone is volatile and cannot be detected in
the blood.
▣ The odour of acetone may be detected in the
breath and also in the urine of a person who
has high level of ketone bodies in the blood.
Eg:diabetic ketoacidosis
● Under normal conditions, acetone formation
is negligible.
16. Regulation of Ketone body synthesis:
Regulatory enzyme–HMG COA synthase
Induced by -increased fatty acids in the
blood.
Inhibitor- CoA-SH
17. Importance of Ketogenesis
● Starvation when carbohydrate store are
depleted and oxidation of fats becomes a
major source of energy to the body.
● The brain normally uses glucose as the
only fuel. After the diet has been changed to
lower blood glucose for 3 days, the brain
gets 25% of its energy from ketone bodies.
After about 40 days, this goes up to 70%,
but can not utilize FA.
18. KEKetolysisKE
Ketolysis
● Complete oxidation of ketone bodies to C02
and water.
Site:
● Mitochondria of extrahepatic tissues
(high activity of the enzyme thiophorase)
● Not in the liver due to deficiency of this
enzyme
19.
20. ● During prolonged starvation ,brain and skeletal
muscle may utilize ketone bodies as alternate
sources of energy..
● Heart muscle and renal cortex prefer ketone
bodies to glucose as fuel.
● RBCs and liver cannot oxidise ketone bodies.
21.
22. Ketosis
▣ It is the accumulation of the ketone
bodies in the blood (Ketonemia) and
their appearance in the urine (ketonuria)
together with acetone odour in the breath
and acetone can be detected in urine.
24. Diabetic ketoacidosis
● Untreated diabetes mellitus -most common
cause
● The deficiency of insulin causes accelerated
lipolysis More fatty acids are released into
circulation Oxidation of these fatty acids
increases the acetyl-CoA pool Oxidation of
acetyl-CoA by TCA cycle is reduced, since
availability of oxaloacetate is less.
25. Starvation
● The dietary supply of glucose is decreased.
● Available oxaloacetate is channelled to
gluconeogenesis.
● The increased rate of lipolysis is to provide
alternate source of fuel.
● The excess acetyl-CoA is converted to
ketone bodies.
● The high glucagon favors ketogenesis.
26. Hyperemesis (vomiting) in early
pregnancy may also lead to
starvation-like condition and may
lead to ketosis.
