1. Dr. Ifat Ara Begum
Assistant Professor
Dept of Biochemistry
Dhaka Medical College
2.
3. Organic acid containing a long
hydrophobic hydrocarbon chain and a
terminal carboxyl group.
They exist free in the body as well as
fatty acyl esters in more complex
molecules such as triglycerides or
phospholipids.
Fatty acids can be oxidized in all tissues,
particularly liver and muscle to provide
energy
4. They are also structural components
of membrane lipids such as
phospholipids and glycolipids.
Esterified fatty acids, in the form of
triglycerides are stored in adipose
cells
Fatty acids are also precursors of
Eicosanoids.
5.
6.
7. Diet
Adipolysis
De novo synthesis(from precursors)-
Carbohydrates, protein, and other
molecules obtained from diet in
excess of the body’s need can be
converted to fatty acids, which are
stored as triglycerides
8. 1. a source of carbons, specifically
acetyl-CoA
2. a source of reducing equivalents,
specifically NADP2H
9. Compartment: Cytoplasm
Site: liver, kidney, brain, lung,
mammary gland, and adipose tissue.
Substrate: Acetyl-CoA
End product: free palmitate (16-C
Palmitic acid), which can be
elongated/shortened with/without
desaturation to synthesize diff types of
FA as per body need.
10.
11.
12. Nature: Anabolic
Rate limiting enzyme: Acetyl CoA
carboxylase
ATP required: 7 ATP for 1 molecule of
Palmitic acid.
Specialty: Reductive synthesis process
Hormonal Control: Insulin promotes but
glucagon & catecholamine inhibit.
13. Two main enzymes-
Acetyl co A carboxylase
Fatty acid Synthase
Both the enzymes are multienzyme
complexes
Coenzymes and cofactors are-
Biotin
NADPH
Mn++
Mg++
14. Catalyzes the Initial & Controlling Step
in Fatty Acid Synthesis.
Multienzyme complex containing-
Biotin: Enzyme prosthetic group
Biotin Carboxylase
Biotin carboxyl carrier protein
Transcarboxylase
A regulatory allosteric site
15. FAS is a polypeptide chain with
multiple domains, each with distinct
enzyme activities required for fatty
acid biosynthesis.
Here the activator is a protein called
the acyl carrier protein (ACP). It is part
of the FAS complex. The acyl groups
get anchored to the CoA group of ACP
by a thioester linkage
16. Condensing enzyme/β-ketoacyl
synthase (K-SH): Also part of FAS, CE
has a cysteine SH that participates in
thioester linkage with the carboxylate
group of the fatty acid. During FA
biosynthesis, the growing FA chain
alternates between K-SH and ACP-SH.
17. Fatty acid biosynthesis is a
stepwise assembly of acetyl-CoA
units (mostly as malonyl-CoA)
ending with palmitate (C16
saturated)
18. The fatty acid molecule is synthesized 2
carbons at a time. The synthesis begins
from the methyl end and proceeds toward
the carboxylic acid end. Thus, C16 and
C15 are
added first and C2 and C1 are added last.
C15 and C16 are derived directly from
acetyl-CoA. For further step-wise 2-
carbon extensions, acetyl-coA is first
activated to malonyl CoA, a 3-carbon
compound, by the
addition of a CO2.
19.
20. FAs are synthesized in the cytoplasm from
acetyl-coA, which is generated from Pyruvate
by the action of PDH and by β-oxidation of
fatty acids in the mitochondria. This acetyl-coA
is transported from mitochondria to
cytoplasm via Citrate Shuttle.
Acetyl-coA condenses with OA to form citrate
by citrate synthase. A tricarboxylate
translocase transports citrate from
mitochondria to cytosol.
In the cytosol, citrate breaks up to OA &
acetyl-CoA by citrate lyase with hydrolysis of
one molecule of ATP. OA is converted back to
Pyruvate for re-entry into mitochondria
21. It involves the following steps :
Activation of acetyl CoA: Acetyl-CoA
carboxylation
Elongation of FA chain: The malonyl-CoA
pathway which consists of a condensation
step, a reduction step, a dehydration
step, then another reduction step. The
cycle is then repeated.
Termination of FA synthesis
22. Activation of each acetyl CoA:
Acetyl CoA + CO2 -> Malonyl CoA
Reaction catalyzed by Acetyl CoA
Carboxylase
23.
24. This is an irreversible reaction.
AcetylCoA carboxylation is a rate-limiting
step of FA biosynthesis.
AcetylCoA carboxylase is under
allosteric
regulation. Citrate is a positive effector
and palmitoyl CoA is a negative
effector.
25. Selection of acetyl CoA as primer and
its attachment with FAS.
Elongation of FA chain by repeated
addition of 2-C fragments from
malonyl CoA to the primer and its
growing chain. Each time 2 NADP2H is
used to provide hydrogen & it is
catalyzed by FAS.
26. Each malonyl- CoA pathway consists of a
condensation step, a reduction step,
a dehydration step, then another
reduction step
Each cycle through the malonyl-CoA pathway
results in two carbons being added to the FA
chain.
The steps involved in the malonyl-CoA
pathway occur with the growing FA chain
esterified to an acyl carrier protein.
27.
28. It occurs when 16-C Palmitic acid is
formed by seven (07) repeated turns.
Net Reaction for synthesis of 16-C
Palmitic acid:
8 Acetyl-CoA + 7 ATP+ 14 NADP2H -
>
Palmitic acid + 7 CO2 + 14 NADP +
7 ADP
29. First, the formation of seven malonyl-
CoA molecules:
7Acetyl-CoA + 7CO2 + 7ATP->
7malonyl CoA + 7ADP + 7Pi
30. Then the seven cycles of condensation
and reduction
Acetyl-CoA + 7malonyl-CoA +
14NADPH + 14H+ -> palmitate + 7CO2
+ 8CoA + 14NADP+ + 6H2O