KAFUE INSTITUTE OF

HEALTH SCIENCES AND

RESEARCH
DIPLOMA IN PHARMACY
BIOCHEMESTRY
{LIPID METABOLISM}

ZULU WILLIAM
movingcollege35@gmail.com
 TOPIC OUTLINE
INTRODUCTION

 β-oxidation of fatty acids in

mitochondria

Ketone Bodies
 Introduction to fatty acid catabolism
• Fatty acid oxidation provides 80% of the
energy in mammals.
• Fatty acid chains get oxidized to water and
CO₂ and their electrons pass onto the
electron transport chain (ETC).
• Acetyl CoA produced during fatty acid
metabolism can either enter the citric acid
cycle or be converted to ketone bodies
(utilized by organs such as brain when
glucose is not available).
• Fatty acid oxidation serves many
purposes e.g. in plants its mostly for
formation of precursor molecules primarily
and secondarily as fuel source.

• Despite this B-oxidation steps are the

same in organisms.

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 Introduction to fatty acid catabolism

In the cells, more mechanisms are needed

to mobilize the stored fats and transport
them into the mitochondrial matrix for β-
oxidation.
 Introduction to fatty acid catabolism

• Vertebrates use fats from diet, fats stored

in adipose tissue and fats made from
conversion of extra glucose into fat.
• Fats are hydrophobic while enzymes
responsible for their breakdown are water
soluble.
• They need to be solubilized in order to be
absorbed into the intestinal wall.
• Bile salts turn insoluble fat globules into
dispersed micelles (increasing contact
between molecules and enzymes).

• Hormones signal release of fatty acids

from cells to metabolizing tissue such as
skeletal muscle, heart and kidney (renal
cortex). Epinephrine and glucagon
(response to low sugar levels).

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Fatty Acid transport from dietary intake to cells
 Β- Oxidation
Mitochondrial oxidation involves 3 stages;
1.Oxidative removal of 2 carbon units (acetyl
CoA) from the COOH end of fatty acid.
2. Acetyl CoA produced goes through the
citric acid cycle for further oxidation to CO₂.

3. NADH and FADH₂ donate their electrons to

the electron transport chain, producing ATP.
 B-OXIDATION
• Fatty acid break down occurs in
three stages;
1. 2 carbons are successively
removed in form of acetyl CoA.
This starts from COOH end. So
a 16 carbon fatty acid will yield
8 acetyl CoA molecules (i.e.
passes through this process 7
times). NADH and FADH2 are
also produced during each
 B-OXIDATION

2. Acetyl CoA units

produced go through the
citric acid cycle yielding
more NADH and FADH2.
 B-OXIDATION
3. FADH2 and NADH produced from the first two
stages pass through the electron transport chain
in the mitochondrial matrix, creating ATP.
B-Oxidation pathway

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 B-Oxidation
• The first stage of fatty acyl
chain involves acyl CoA
dehydrogenase which has
an FAD prosthetic group.
(3 isozymes work on 12-
14, 4-14 and 4-8 carbon
chain lenths).Bond
between C2 and C3 is
dehydrogenated to create
trans double bond
(essential orientation for
the next enzyme).
 B-Oxidation

• The second step involves

hydration of the double
bond by enoyl CoA
hydratase to create β-
hydroxyacyl CoA.
 B-Oxidation

• Next, L-β hydroxyacyl CoA

is dehydrogenated by β
hydroxyacyl CoA
dehydrogenase to form β-
ketoacyl CoA.
• Electrons are transferred
and carried by NAD+
which is loosely bound to
the enzyme.
 B-Oxidation
• Finally acyl CoA acetyl transferase (thiolase)
enzyme catalyzes the reaction between B-
ketoacyl CoA with free CoA.
• CoA facilitates hydrolysis of bonds.
• CoA thioster bond is formed on the remaining
fatty acid chain.
 B-Oxidation
• Two sets of enzymes catalyze the last 3
reactions with enzyme employed depending
on the fatty acid chain length.

• With 12 or more carbons are catalysed by

multi enzyme complex Trifunctional
Protein(TFP).

• Fatty acid chains 12 carbons or shorter are

acted on by single enzymes that are
dissolved in the matrix.
 B-Oxidation
 One oxidation sequence yields 4H⁺(carried in FADH₂,
NADH and H⁺).
 For example;

 Acetyl CoA is also yielded

after each oxidation sequence.
 B-Oxidation
• Each FADH₂ donates 1 electron pair to the ETC-
yields 1.5 ATP molecules.
• 2.5 ATP yielded per NADH electron pair transfer.
• So total of 4 ATP per 1 cycle of fatty acid
oxidation where 2carbon units are removed.
• The overall reaction for Palmitate would be;

• Remember NADH + H⁺ + ⅟2 O₂ NAD⁺ + H₂O

 B-Oxidation
• Now lets consider the energy yield per
molecule of acetyl CoA;
• Acetyl CoA enters the citric acid cycle.
 B-Oxidation
• Each acetyl CoA yields the following;

2CO₂ X8 = 16 CO₂
1 FADH₂ (1.5 ATP) x 8 = 12 ATP
3NADH (2.5 ATP X 3) x 8 = 60 ATP
1GTP (1 ATP) x 8 = 8 ATP

• (1 FADH₂ + 3NADH + H⁺ + 2O₂) X 8 i.e. 16O₂ that are

reduced to 16H₂O.
 KETONE BODIES
• Fatty acid metabolism is triggered in parts
by response to low glucose levels.
• Although there is an abundance of acetyl
CoA, intermediates of citric acid cycle are
channeled into gluconeogenesis.
• Also each cell has limited amounts of
Coenzyme A (CoA).
• This means cell has to find alternative ways
to ensure the large amounts of acetyl CoA
are oxidized.
 KETONE BODIES
• So while some acetyl CoA goes to Citric
Acid cycle some is converted into ketone
bodies in the liver (brain can use this as
alternative fuel source when glucose is low).
• All organs except liver use this as fuel.
• Ketone bodies examples: acetoacetate,
acetone and β-hydroxybutyrate.
• Acetone is volatile(evaporate easly) and can
be detected in the breathe-(sometimes
used to diagonise diabetes).
 KETONE BODIES
• Formation of ketone bodies frees up
coenzyme A so fatty acid oxidation can
continue.
• Ketone bodies travel in blood to
extrahepatic (outside the liver) cells.
• The liver makes these ketone bodies but
lacks enzymes that convert these ketone
bodies to acetyl CoA so it cannot use
ketone bodies for energy.
• Ketone bodies are overproduced in
diabetes and during starvation.
• Starvation and untreated diabetes
mellitus lead to overproduction of
ketone bodies, with several
associated medical problems.
• The increased blood levels of
acetoacetate and D-beta-
hydroxybutyrate lower the blood pH,
causing the condition known as
acidosis. Extreme acidosis can lead to
coma and in some cases death.
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