-oxidation and

ketogenesis
Biochemistry lecture
 Outcomes
• Describe beta oxidaton, ketogenesis and
ketone bodies utlizaton
• Discuss the role of insulin & glucagon in
regulaton of these metabolic pathways
 -oxidaton
 It is the catabolic process by which faty acid molecules are
broken down in the mitochondria to generate energy.

 Tissues  Liver, Sk. Muscles, Kidneys

 I/C site  Mitochondria

 Aerobic  Requires O2

 Generates  ATP
 Products  Acetyl CoA + NADH + FADH2
 Stimulates Gluconeogenesis
The enzymes of Gluconeogenesis are stimulated by high
levels of acetyl-CoA (produced in β-oxidation in the liver)
-oxidaton – Actvaton of faty acid
.-oxidaton – Translocaton of f.a
-oxidaton - overview
-oxidaton
 Cycles of -Oxidation

The length of a faty acid:

• Determines the number of oxidations and
• The total number of acetyl CoA groups.
Carbons in Acetyl CoA -Oxidation Cycles
Faty Acid (C/2) (C/2 –1)
12 6 5
14 7 6
16 8 7
18 9 8
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 -Oxidation and ATP

Activation of a faty acid requires:

• 2 ATP
One cycle of oxidation of a faty acid produces:
• 1 NADH 3 ATP
• 1 FADH2 2 ATP
Acetyl CoA entering the citric acid cycle produces:
• 1 Acetyl CoA 12 ATP

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-oxidaton
 Ketone bodies
 Also called ‘Acetone
bodies’

 “Ketone” should not be

used

 Under certain
conditions , liver
produce excess amount
of ketone bodies which
can be degraded as
alternative fuel for cells
 Ketone bodies are produced by the liver during
periods of caloric restriction of various scenarios:

1- low food intake (fastng)

2-carbohydrate restrictve diets
3-starvaton
4-prolonged intense exercise
5-alcoholism
6- during untreated (or inadequately
treated) type 1 diabetes mellitus.
 Ketone bodies
 Acetoacetate & -OH
butyrate are
interconvertable

 Interconversion is
controlled by
mitochondrial
NAD+/NADH

 Soluble in plasma

 Spare glucose as fuel

 Ketogenesis
• Synthesis of ketone bodies
from excess Acetyl COA
• HMG CoA synthase is the
rate limiting step

• Occurs only in liver

• N  3 mg/dl

• Can be utilized as fuel even

by brain
Ketogenesis
.Formaton, utlizaton & excreton of K.B
.Formaton, utlizaton & excreton of K.B
 :Ketolysis

• It’s the process of oxidaton of ketone bodies

into CO2 and water (release energy).
• Site : mitochondria of the extra hepatc
tssue , never occurs in the liver because the
transferase is absent in liver.
• In case of prolonged fastng extra hepatc
tssue and even the brain can use ketone
bodies
 Ketolysis

After 5-6 days of fasting the brain cannot oxidize fatty

acids but can use ketone bodies as fuel as they are

transported across the inner mitochondrial membrane as

well as across the blood-brain barrier and cell membranes

 Regulaton of ketogenesis
  FFA level

 Transport of faty acids through

the mitochondrial membrane is an
important regulatory point.

 CPT-I  stimulated by
 Starvation
  insulin/glucagon

 inhibited by
 Sulfonylurea drugs
 Regulaton of ketogenesis
During fastng the ant-insulin hormones are stmulated
lipolysis is actvated.
This produce excess Acetyl COA which form ketone bodies

Ketolysis is stmulated in case of decrease availability of

glucose oxidaton requirements (oxaloacetate) as during
prolonged starvaton and ant-insulin hormone stmulaton

During prolonged starvaton, oxalacetate is low, due to

excess gluconeogenesis, so Acetyl CoA from fat/protein
catabolism does not go to TCA, but rather to ketone body
producton