lipogenesis

1. Dr. Ifat Ara Begum
Assistant Professor
Dept of Biochemistry
Dhaka Medical College

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.

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.

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.

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

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.

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

31. Glycerol-P
Triacylglycerols
Fatty acyl CoA
Malonyl CoA
Glucose
Pyruvate
Acetyl CoA
TCA cycle