Biosynthesis of

Fatty acids
OBJECTIVE:
Understand the metabolic pathway
of lipids.
 Occurrence of
Biosynthesis of • GLUCOSE enters into the liver
Fatty Acids
üFed State
üHigh Blood Glucose
ØINSULIN- helps
the metabolism of
fatty acid
ü High production of
ATP (our body stop
breaking molecules
instead stored and
build up and use it
later)
 Occurrence of
Biosynthesis of Fatty
Acids
NADP+ NADPH
Citrate Lyase break the citrate into two
molecules Oxaloacetate (OAA) which is
Malic enzyme originally coming from Acetyl-CoA and
Malate oxaloacetate.
OAA
Important in Fatty acid synthesis
Acetyl CoA
CoASH is a coenzyme, well known for it's role
added in the synthesis and oxidation of fatty
acids, and the oxidation of pyruvate in
Citrate Lyase the citric acid cycle
take and cut the
citrate to OAA+
Acetyl CoA and
to malate to
pyruvate.
Too much ATP production our
body has a way to regulate this
process.
ATP is responsible for
allosterically inhibiting
isocitrate dehydrogenase
enzyme.
Resulted to the build up of D
Isocitrate and it is reversible
and start producing
significantly large amount of
citrate.
Citrate can pass through
mitochondrial membrane.
2 types of regulation:
1. Allosteric When stimulated w/ processes by
a. citrate + citrate +, but when activate the
Dimers of ACC citrate, the dimers will become
b. Long Chain Fatty Acid w/ Inactive forms
CoA - Citrate+ stimulating tofuse
drive together. When they are
2. Hormonal
this reaction polymerized together
a. insulin+ c. epinephrine they are in active form-
b. glucagon d.) Norepinephrine Long Chain Fatty Acid COAPolymerized form of ACC
stimulating to drive this reaction
Acetyl-Coenzyme A
Carboxylase (ACC) highly • But one does not drive this reaction it does an opposite
regulated Citrate+ stimulating to drive way from polymerized form of ACC (active)to dimers of
this reaction ACC (inactive).
Precursor of fatty
acid • It is stimulated by Long Chain Fatty Acid CoA.
CO2 added by
ACC Sources of reducing agent are:
Acetyl CoA (Carboxylation through oxidative phase.
process) 1. Malic enzyme
2. Pentose phosphate pathway
 G protein-coupled
Opposer
receptor (GPCR)
1.Insulin wants to build things up such
e
as fat, protein and in

ls
r e

ro
ph n hrin

gly A)
Glycogen
e

ce
in ago ep

yl PK
2. epinephrine p
e uc pin

ac (
glucagon

tri se A
Norepinephrine
gl ore
N

lin

nd ina
-this is stress situation that wants to break

sa k
su
down lipids and glycogen

id in
Phosphoprotein Phosphatase

In

ac rote
stimu

p
ate late
tr
Ci

tty
PP

Fa
PP

of
sis PP
Inactive Active form
he

form ACCPP ACC

t
yn

P
(dimer) PPP (polymer)
os
Bi

tty acid
Long chain fa phosp
hate

protein kinase A (PKA)

phosphorylate the active form
e
hri n ne
ep n r i
pin ago eph
e uc pin
gl ore
N
 CPT2 gene provides instructions for making an enzyme called carnitine
palmitoyltransferase 2. This enzyme is essential for fatty acid oxidation, a multistep
process that breaks down (metabolizes) fats and converts them into energy.

Malonyl-CoA is an
inhibitor of carnitine
palmitoyltransferase.
Thus, high levels of
Fatty acid malonyl-CoA suppress
fatty acid entry into the
mitochondria and this in
turn leads to increased
Carnitine palmitoyltransferase 1 (CPT1) flux of fatty acids to
Regulate the activity of triglycerides.

3 component of fatty acid synthesis

CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial 1. NADPH –reducing power
inner membrane and its deficiency results in a decreased rate of fatty acid beta- 2. Malonyl CoA- building block to
oxidation.
make FA
When fatty acid enters into mitochondria 3. FAS I
will go through to the process beta
oxidation to make ATP
fatty acid synthase (FAS) type 1
2 enzyme
cysteine residue thiol
that is
FAS catalyzes all the reaction utilize to
steps in the conversion make fatty
of acetyl-CoA and malonyl- acyl carrier protein (ACP) sulfhydryl group acid
CoA to palmitate
Acyl carrier protein (ACP) is a universal and
highly conserved carrier of acyl intermediates
during fatty acid synthesis.
 ACP attach is Beta The Beta ketoacyl ACP
Ketone purpose is to hydroxyl reductase will take
take and spread beta attached to the beta ketone ACP
ketone and electrons in beta ketone group and converting
the form of hydride it to hydroxyl group
CoA ions Dropped the electron in hydride form

SH SH

acetyl transacylase
Beta ketoacyl ACP reductase

acyl transacylase
CoA 3-hydroxyacyl dehydrogenase

CoA
malonyl transacylase enzyme
CO2 ENOYL enoyl acp reductase
SH
decarboxylayion
Acyl Malonyl ACP SH
Condensing acyltraferases
Enzyme
Beta Ketone

Since it need only 4 carbon one carbon is plucked off. The 2 carbon from cyst will
condensed to 3 carbon in ACP, but before it condenses one carbon will pop off in the
form of CO2 Take the hydroxyl group pull GET RAID OF DOUBLE GET RAID OF DOUBLE
BOND IN ENOYL GET THE BOND IN ENOYL GET THE
it out and formed into water HYDROGEN ELECTRONS HYDROGEN ELECTRONS
and dehydrate this molecule. FROM NADPH FROM NADPH to form CH2
 CoA

CoA
malonyl transacylase enzyme
CO2 SH

Acyl Malonyl ACP Condensing Enzyme

 Biosynthesis of
Triacyl
Glycerol/Triglyce
ride(Lipogenesis)
OBJECTIVE:
Understand the metabolic pathway
of lipids.
 Glycolysis

dihydroxyacetone phosphate (DHAP)

NADH
NADP+
From Adipose Tissue

1
Lipolysis 2
3

Fatty Acly CoA’s

 Glycolysis

dihydroxyacetone phosphate (DHAP)

e
From Adipose Tissue NADH + inas
NAD l K
o
cer
ly
1 G
Lipolysis 2
3 Poy3-
Poy3-
Glycerol-3-phosphate
Fatty Acly CoA’s
 Acyl transferase
1

CoA
2

3 Poy3-
 MAG

1 Lysophosphatidic acid

3 Poy3-
1 Lysophosphatidic acid
Acyl transferase
2

CoA
3 Poy3-
1
Lysophosphatidic acid

2
Phosphatidic acid
DAG
3 Poy3-
1
Lysophosphatidic acid

2
Phosphatidic acid

3 Poy3-
Acyl transferase

CoA
Poy3-
Phosphatase
 Triglyceride/TAG triacyl glyceride

1
Lysophosphatidic acid

2
Phosphatidic acid

3 Lysophosphatidic acid
Resynthesize
back to
triglyceride
Package to VLDL and transported to adipose tissue Where they
can be stored
in adipose
tissue
Thank You!!