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What is this sort of a diet?

KETOGENESIS
SPECIFIC LEARNING OBJECTIVES
At the end of the session, you will be able to

1. List the types of ketone bodies

2. Indicate the conditions in which their


synthesis is favored

3. Describe the steps of ketogenesis


KETONE BODIES
• Water-soluble, transportable form of acetyl units
• Source of energy : Cardiac muscle, kidneys, brain

20% Acetoacetate

78% Beta hydroxy butyrate 2% Acetone


KETONE BODIES
• Energy source for tissues during
» Starvation
» Uncontrolled Type 1 Diabetes Mellitus
» Low carbohydrate with high fat diet

• Circulatory level of ketone bodies :


In a normal well fed person  ≤ 1mg/dl
In prolonged starvation  up to 500mg/dl
MECHANISM
Glucose Fatty acids
G LYC O LY S I S β - O X I D AT I O N

Pyruvate Acetyl CoA


GLUCONEOGENESIS

Oxaloacetate

TCA CYCLE
MECHANISM
• INSULIN
STARVATION

UNCONTROLLED TYPE 1 DM • GLUCAGON


• EPINEPHRINE

LOW CHO • GROWTH


HIGH FAT DIET HORMONE
MECHANISM
Glucose Fatty acids
G LYC O LY S I S β - O X I D AT I O N

Pyruvate Acetyl CoA


GLUCONEOGENESIS

Oxaloacetate Ketone Body


Synthesis

TCA CYCLE
KETOGENESIS
• Site : Liver (90%), Kidney (10%)

• Cellular site : Mitochondria

• Substrates : Acetyl CoA

• Products :
Acetoacetate – Primary
Betahydroxy butyrate & Acetone – Secondary
KETOGENESIS
Acetyl CoA Acetyl CoA

Thiolase CoA-SH

Aceto-acetyl CoA Acetyl CoA


Rate – limiting
H₂O
HMG CoA synthase CoA-SH

HMG CoA
(3-Hydroxy 3-methyl glutaryl CoA)
KETOGENESIS
HMG CoA
HMG CoA lyase Acetyl CoA

Acetoacetate
NADH + H⁺ Non-enzymatic
Dehydrogenase decarboxylation
NAD CO₂

Beta hydroxy butyrate Acetone


KETOGENESIS
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SUMMARY
• Ketone bodies are a major source of energy
during starvation and uncontrolled type 1 DM

• The ketone bodies are acetoacetate, acetone


and beta-hydroxybutryate

• Synthesized in liver mitochondria

• Rate limiting enzyme is HMG CoA synthase


Thank you…

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