Ketone
bodies and their utilization
Objective
• At the end of this lecture, student
will be able to
– Explain ketogenesis and Ketolysis
– Describe the disorders associated
with ketone bodies
Ketone bodies
• Acetone, Acetoacetate &
β-hydroxybutyrate are known as ketone bodies
• Only the first two are true ketones
while β-hydroxybutyrate does not possess a keto (C=O)group
• Ketone bodies are water-soluble and
energy yielding
• Acetone, however, is an exception,
since it cannot be metabolized
Ketogenesis
• Synthesis of ketone bodies is known
as Ketogenesis
• Occurs in Iiver
• Enzymes are Located in mitochondrial
matrix
• Acetyl CoA, formed by oxidation of
fatty acids, pyruvate or some amino acids, is the precursor for ketone bodies
• The main purpose of ketogenesis in
the liver is to distribute excess fuel (Acetyl-CoA) to other tissues.
Ketogenesis occurs through the following
reactions
1. Two
moles of acetyl CoA condense to form acetoacetyl CoA, This reaction is catalysed by thiolase, an
enzyme involved in the final step of β-oxidation
2.
Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β-hydroxy β-methyl glutaryl CoA (HMG CoA),
catalysed by HMG CoA synthase
3. HMG CoA
lyase cleaves HMG CoA to produce acetoacetate and acetyl CoA
4. Acetoacetate
can undergo spontaneous decarboxylation to form acetone
5.
Acetoacetate can be reduced by a dehydrogenease to β-hydroxybutyrate
Ketolysis
• Degradation
of ketone bodies
• Ketone
bodies produced in the liver reach peripheral tissues through circulation
• Heart,
kidney, cortex, brain and to a certain extent skeletal muscle uses ketone
bodies for energy
Biological
significance
• Heart,
kidney and cortex prefer to use ketone bodies rather than glucose.
• During
prolonged starvation, brain derives most of the energy from ketone bodies
• Liver
is unable to use ketone bodies due to lack of enzymes.
Utilization of Ketone bodies
• Ketone bodies, being water-soluble,
are easily transported from the liver to various tissues
• Acetoacetate and β-hydroxybutyrate
serve as important sources of energy for the peripheral tissues such as skeletal muscle, cardiac muscle/
renal cortex etc
• During prolonged starvation, ketone
bodies are the major fuel source for the brain and other parts of central
nervous system
• The production of ketone bodies and
their utilization become more significant when glucose is in short supply to
the tissues, as observed in starvation, and diabetes mellitus
Disorders
• The concentration of ketone bodies
in blood is maintained around 1 mg/dl
• Their excretoin in urine is very low
and undetectable by routine tests (Rothera’s test)
• When the rate of synthesis of ketone
bodies exceeds the rate of utilization, increased concentration in blood known
as ketonemia
• Ketonuria represents the excretion
of ketone bodies in urine
• Hyper ketonemia and ketonuria gives
rise to ketosis (Smell of acetone in breath is a common feature in ketosis)
• Ketosis is most commonly associated
with starvation and severe uncontrolled diabetes mellitus,
• The hormone glucagon stimulates
ketogenesis whereas insulin inhibits it
• Ketoacidosis: Both acetoacetate and β-hydroxybutyrate are strong acids. Increase in their concentration in
blood would cause acidosis
• Diabetic ketoacidosis is dangerous,
may result in coma and even death if not treated
Summary of ketone bodies synthesis, Utilization and excretion
Summary
• Ketogenesis
is synthesis of ketone bodies
• Take
place in liver and major source of energy
• Acetone,
Acetoacetate and β-hydroxybutyrate are 3 ketone bodies
• Increased concentration in blood
known as ketonemia
• Ketonuria represents the excretion
of ketone bodies in urine
• The overall picture of ketonemia and
ketonuria is commonly referred to as ketosis
• The hormone glucagon stimulates
ketogenesis whereas insulin inhibits it.