Ketone bodies and their utilization

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.

 

 

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