4 LipidMetab Nutrition LLR - 230220 - 102056

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LIPID BIOSYNTHESIS/LIPOGENESIS
Dr. dr. Lina Lukitasari, M.Si
Team Teaching Medical Biochemistry
Departement of Physiology and Medical Biochemistry

Medical Faculty, Airlangga University
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Lipid biosynthesis
• The goal for lipid synthesis are for obtaining a variety of
lipids in the body with their respective biological
functions,
• The body can synthesize many types of lipids, except for
essential FA (Only two fatty acids are known to be essential for
humans: alpha-linolenic acid (an omega-3 FA) and linoleic
acid (an omega-6 FA).
• The biosynthetic process is also a tool to convert excess
calorie sources into lipids for storage in adipose tissue (On a
high-carbohydrate diet  The excess glucose is synthesized into
FA).
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FATTY ACID
BIOSYNTHESIS
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Fatty acid biosynthesis

• Fatty acids (FA) is an important compound in the body
that must always be able to provide.
• FA source:
• from the diet (exogenous sources)  mechanism for the
absorption of lipids from the gastrointestinal tract  the
mechanism for transporting lipids between tissues
• from endogenous sources:
• from their own formation (synthesis):
• De novo synthesis = The formation of new FA from non-lipid compounds.
• Chain lengthening/elongation from existing FA = The addition of bicarbon
units to convert existing FA into longer FA.
• Desaturation = The provision (pengadaan) of double bonds in the
hydrocarbon groups (alkyl groups) of FA.
• and from lipolysis of TG (convert TG into FA) that is stored in adipose
tissue.
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ENDOGENOUS SOURCES FA:

DE NOVO SYNTHESIS OF FA
New Fatty acid biosynthesis
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De Novo Synthesis of FA
• De novo synthesis
has a more
important role than
just meeting the
body's need for lipids
 process to
convert excess
energy (???....) into
FA  convert FA into
TG  storage TG in
adipose tissue.
• Why is it called De
Novo?
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De Novo Synthesis of FA
• Precursor for de novo
synthesis is Acetyl-CoA
 convert into
saturated Palmitic Acid
(FA with 16 C).
• Why is it called De Novo?
• The process takes place
in the cytosol  Occurs
mainly in the Liver cell
• The reactions proses
look like a series of
reversed beta-oxidation
reactions:
• The enzymes
• The process place
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Basic Flow of Synthesis de Novo FA

• Acetyl (2 C atoms) + Malonyl (3 C
atoms)  release of CO2
(decarboxylation) from the malonyl
group. A compound with 4 atoms of
C (2 + 3 – 1= 4) is formed.
• Malonyl functions as an addition
to the bicarbonate unit
• 1st process hydrogenation,
dehydration, and hydrogenation
occur to form an acyl group (4 C).
• The process will continue to repeat
until an acyl-CoA with 16 C atoms
(palmitoyl-CoA) is formed.
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CHAIN LENGTHENING/ELONGATION
FA biosynthesis
Chain lengthening = The addition of bicarbon
units to convert existing FA into longer FA.
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Elongation of Fatty Acid Chains Occurs in

the Endoplasmic Reticulum
• This pathway (=the “microsomal
system”) elongates saturated and
unsaturated acyl-CoAs
• Adding two carbons using
malonyl-CoA as
• NADPH>NADH as the H+ donor
• Catalyzed by the microsomal
fatty acid elongase system
enzymes
• FA Saturated (<16 atom C)  The
main Product is Stearat ( 18:0)
• FA Unsaturated C >18  The
main Product is 26 Atom C
• Maximum elongation 26 Atom
C  Important for myelination of
neuron brain (provide C22 and
C24 FA for sphingolipids).
Microsomes (=vesicles formed by the

membrane of the endoplasmic reticulum).
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Elongation of Fatty Acid Chains Occurs in

Mitochondria
• Similar to reverse beta oxidation
• Hydrogen donors: NADPH and NADH
• Adder 2 atoms C : Acetyl-CoA
• When the NADH:NAD ratio ↑ (ATP ↑)  chain elongation ↑
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FA DESATURATION
Fatty acid biosynthesis
Desaturation = The provision of double bonds
in the hydrocarbon groups (alkyl groups) of
FA.
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FA Desaturation
• Saturated FA from food (exogenous) Converted to unsaturated FA
• Saturated FA endogenous Converted to unsaturated FA
• The main characteristics of desaturation in humans:
• Saturated FA that can be desaturated are FA that have 16 C atoms.
• The first double bond is always formed between C atom number 9 and
number 10 (counting from the carboxyl end).
• Second double bond and so on: Towards the carboxyl group with a distance of
3 C atoms (methylene group CH-CH2-CH) from the previous double bond
CH3….C=C-C-C=C-C-C=C…..COOH
9 10 to this way
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Proses desaturasi FA dapat

berlangsung berulang-ulang
atau
proses desaturasi berlangsung
berselang-seling dengan
proses pemanjangan rantai.
The FA desaturation process

can take place repeatedly or
the desaturation process can
take place alternately with the
chain elongation process.
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FA ESSENSIAL
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FA ESSENSIAL
• Cannot be synthesized by the

body but is required by the
body:
• Only two FA are known to be
essential for humans:
• Alpha-linolenic
acid (an omega-3 FA) and
• Linoleic acid (an omega-6 FA)
• These essential FA are usually
esterified with phospholipids
 can be released from
phospholipids (lipolysis)  as
precursors to form various
eicosanoids (prostaglandins,
thromboxanes and leukotrienes).
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FA ESSENSIAL
• These substances are important because ther function,
among other things, as hormones, mediators of
inflammation, and agents of blood clotting. 
Essential FA are required from the diet in relatively small
amounts.
• Clinical Symptoms of deficiency in normal daily diets are
rare, except patients receiving long-term parenteral
nutrition
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FA ESSENSIAL
Linoleic acid Alpha Linolenic acid
• 18:2 (ω-6) or 18:2 cis- • 18:3(ω -3) or 18:3 cis-

9,12. 9,12,15
• PUFA • PUFA
• It is a colorless or white • ALA is found in many
liquid seeds and oils,
• It typically occurs in including flax seed (biji
nature as a TG (ester rami), walnuts
of glycerin) rather than (kenari), chia, and many
as a free fatty acid. common vegetable oils.
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BODY FATTY ACIDS

TG = Triasilgliserol = Trigliserida
PL = Phospholipid
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TG BIOSYNTHESIS
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TG biosynthesis
• TG are synthesized by the body for storage, especially in adipose
tissue and smaller amounts of TG are also stored in the muscles.
• The stored TG must be synthesized by the tissues itself 
because TG cannot penetrate cell membranes (including adipose
tissue cells, intestinal mucosal cells and vascular endothelium).
• TG are also synthesized in the liver  transported by lipoproteins
to body tissues.
• The mammary glands also synthesize TG  excreted with milk for
infant nutrition.
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Triasilgliserol (TG)
a
a
a
Molecular structure of TG synthesis
requires:
• "active glycerol" in the form of glycerol Glycerol 3-phosphate
3-phosphate, and supply problem
• "active fatty acids" in the form of acyl-
CoA.
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Active glycerol Supply

Hepar, Kidney, Intestine, The
Adipose tissues and Muscle mammary glands
• Glycerol is phosphorylated using ATP

and the enzyme glycerol kinase.
72
%
12
%
Gb. 6-1. Pencernaan dan absorbsi triasilgliserol di usus
• Do not have glycerol kinase enzymes

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TG biosynthesis
72%
12%
Gb. 6-1. Pencernaan dan absorbsi triasilgliserol di usus

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PL BIOSYNTHESIS
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Phospholipids
• Phospholipids are synthesized by various tissues
• PL is used as components of the cell membranes of these
tissues.
• PL are also synthesized by the liver  to be excreted with
bile (for emulsifying lipids to be digested).
• Alveolar epithelial cells synthesize PL  that function as
surfactants to prevent adhesion of the alveoli during
expiration.
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Phospholipids
a
a
PX
Kolin
Fosfatidilkolin (lesitin) Fosfatidilserin Serin

kepala
ekor
Etanolamin
Fosfatidiletanolamin (sefalin)
Inositol
Fosfatidilinositol
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OH OH
Synthesis of OH
OH
O
O- P
TG and PL
TG and PL have a
glycerol framework 
OH a
a
OH
The early stages of the
synthesis of these two
lipids use the same
metabolic pathway
(reaches the stage of
formation of 1,2-diacyl-
glycerolphosphate).
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TERIMAKASIH

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1

Departement of Physiology and Medical Biochemistry

Fatty acid biosynthesis

ENDOGENOUS SOURCES FA:

Basic Flow of Synthesis de Novo FA

ENDOGENOUS SOURCES FA:

Elongation of Fatty Acid Chains Occurs in

Microsomes (=vesicles formed by the

Elongation of Fatty Acid Chains Occurs in

ENDOGENOUS SOURCES FA:

Proses desaturasi FA dapat

The FA desaturation process

• Cannot be synthesized by the

• 18:2 (ω-6) or 18:2 cis- • 18:3(ω -3) or 18:3 cis-

BODY FATTY ACIDS

Active glycerol Supply

• Glycerol is phosphorylated using ATP

Gb. 6-1. Pencernaan dan absorbsi triasilgliserol di usus

• Do not have glycerol kinase enzymes

Gb. 6-1. Pencernaan dan absorbsi triasilgliserol di usus

Fosfatidilkolin (lesitin) Fosfatidilserin Serin

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