FAT

METABOLISM

Presented by:
1. Maria Binte Eakub : 1812089049
2. Amina Akther Mim: 1821179649
3. Bill Maruf: 1813089649
4. Sajidul Haque Shadh : 1811926649
Key points:

Oxidation of fatty acids

Oxidation pathways

Ketone bodies

Ketosis
 By complete oxidation of 1 gm of Fat produce 9.3
calories energy whereas carbohydrate only 4 cal/gm
Digestion of Dietary Lipids in Vertebrates
Oxidation of Fat
 Oxidation of Fatty Acid

Requires different stges:

1. Activation of fatty acid in cytoplasm
2. Transfer of Acyl CoA from cytosol to mitochondria (Carnitine Shuttle
system)
3. Beta Oxidation in mitochondria
 Dehydrogenation
 Hydration
 2nd dehydrogenation
 Thyolytic cleavage
1. Activation of fatty acid
2. Transfer of Acyl CoA from cytosol to mitochondria
(Carnitine Shuttle system)
3. Beta Oxidation in mitochondria
Fatty Acid Oxidation Pathways

Major Pathway
- β-oxidation

Minor Pathway
- α-oxidation
(branch-chain FA,e.g. Phytanic acid)
- ω-oxidation
 β-oxidation Pathway

4 Major steps:
1. Dehydrogenation (FAD-dependent)
2. Hydration
3. Dehydrogenation (NAD-dependent)
4. Cleavage (Remove 2C as acetyl CoA)
 Number of cycles
n/2 -1 = 7 cycles

Example: Number of acetyl CoA

n/2 =8
Energy of palmitoyl So, 7 NADH, each provide 3 ATP
when oxidized in the ETC
CoA (16 C) oxidation 7X 3= 21 ATP

7 FADH2 each provide 2 ATP

when oxidized in the ETC
7x 2=14
8 acetyl CoAATP, each provides 12 ATP when
converted to CO2& H2O by the TCA
cycle
So total energy yield of oxidation of palmitoyl CoA 8x12= 96 ATP
= 21 + 14 + 96 = 131 ATP
As 2 molecules of ATP are used in the activation
of a molecule of fatty acid Therefore, there is a
net yield of 129 molecules of ATP
Regulation of fatty acid β-oxidation
Oxidation of Odd Numbered Fatty Acid

Oxidation of propionyl-CoA produced by

oxidation of odd-number fatty acids. The sequence
involves the carboxylation of propionyl-CoA to D-
methylmalonyl-CoA and conversion of the latter
to succinyl-CoA.
α-Oxidation Pathway

● In α-oxidation, there is one

carbon atom removed at time
from α position
● Oxidation of phytanic acid
● Enzyme : Hydroxylation
Oxidation
Decarboxylation
 ω-Oxidation Pathway
● This alternative to β oxidation begins
with oxidation of the
● carbon most distant from the α carbon
the ω carbon.
● The substrate is usually a medium-chain
fatty acid; here is lauric acid.
 KETONE BODIES

The entry of acetyl CoA into the citric acid cycle

depends on the availability of oxaloacetate.
The concentration of oxaloacetate is lowered if
carbohydrate is unavailable (starvation) or
improperly utilized (diabetes).
Oxaloacetate is normally formed from pyruvate
by pyruvate carboxylase (anaplerotic reaction).
Fats burn in the flame of carbohydrates.
In fasting or diabetes the gluconeogenesis is activated
and oxaloacetate is consumed in this pathway.
Fatty acids are oxidized producing excess of acetyl
CoA which is converted to ketone bodies:
α-Hydroxybutyrate Acetoacetate Acetone
Ketone bodies are synthesized in liver mitochondria
and exported to different organs.
Ketone bodies are fuel molecules (can fuel brain and
other cells during starvation)
 A. Synthesis of ketone bodies

Two molecules of acetyl CoA

condense to form
acetoacetyl CoA.
Enzyme – thiolase.
Acetoacetyl CoA reacts with
acetyl CoA and water to
give3- hydroxy-3-
methylglutaryl CoA (HMG-
CoA) and CoA.
Enzyme:
HMG-CoA
synthase
3-Hydroxy-3-
methylglutaryl CoA is then
cleaved to acetyl CoA and
acetoacetate.
Enzyme:
HMG-CoA lyase
● 3-Hydroxybutyrate is
formed by the reduction of
acetoacetate by 3-
hydroxybutyrate
dehydrogenase.
● Acetoacetate also undergoes
a slow, spontaneous
decarboxylation to acetone.
● The odor of acetone may be
detected in the breath of a
person who has a high level
of acetoacetate in the blood.
B. Ketone bodies are a major fuel in some tissues

Ketone bodies diffuse from the liver mitochondria into the blood and
are transported to peripheral tissues.
Ketone bodies are important molecules in energy metabolism.
Heart muscle and the renal cortex use acetoacetate in preference to
glucose in physiological conditions.
The brain adapts to the utilization of acetoacetate during starvation
and diabetes.
3-Hydroxybutyrate is oxidized to produce acetoacetate as
well as NADH for use in oxidative phosphorylation.
● Acetoacetate is activated by the transfer
of CoA from succinyl CoA in a reaction
catalyzed by a specific CoA transferase.
● Acetoacetyl CoA is cleaved by thiolase
to yield two molecules of acetyl CoA
(enter the citric acid cycle).
● CoA transferase is present in all tissues
except liver.
● Ketone bodies are a water-
● soluble, transportable form of acetyl
units
 Pathways for Pyruvate
 The pyruvate produced from glucose during glycolysis can be further
metabolized in three possible ways
 For aerobic organisms, when oxygen is plentiful the pyruvate is converted
to acetyl coenzyme A (acetyl CoA)
 For aerobic organisms, when oxygen is scarce, and for some anaerobic
organisms, the pyruvate is reduced to lactate
 For some anaerobic organisms (like yeast), the pyruvate is fermented to
ethanol
 Conversion of Pyruvate to Acetyl CoA
Under aerobic conditions, pyruvate from glycolysis is decarboxylated to produce
acetyl CoA, which enters the citric acid cycle as well as other metabolic pathways
- the enzyme involved is pyruvate dehydrogenase
and the coenzyme NAD+ is also required
This pathway provides the most energy from glucose
 Conversion of Pyruvate to Lactate
• For aerobic organisms under anaerobic conditions, pyruvate is reduced to
lactate, which replenishes NAD+ to continue glycolysis
• During strenuous exercise, muscle cells quickly use up their stored oxygen,
creating anaerobic conditions lactate accumulates, leading to muscle fatigue
and soreness
• Anaerobic bacteria can also produce lactate, which is how we make pickles
and yogurt (among other things)
 Conversion of Pyruvate to Ethanol
● Anaerobic microorganisms such as yeast, convert pyruvate to ethanol by
fermentation
- pyruvate is decarboxylated to acetaldehyde, which is reduced to ethanol
- NAD+ is regenerated to continue glycolysis
● The CO2 produced during fermentation make the bubbles in beer and champagne,
and also makes bread rise
● Alcoholic beverages produced by fermentation can be up to around 15% ethanol
- above that concentration the yeast die
Overview of Pyruvate Pathways