Lipid 1 Lipogenesis 2023
Lipid 1 Lipogenesis 2023
Lipid 1 Lipogenesis 2023
Bagian Biokimia
FK UMSU
TIU & TIK
• Mampu Menjelaskan proses Lipogenesis
• Mampu Menjelaskan proses Elongasi
asam lemak
• Mampu Menjelaskan proses desaturasi
asam lemak
• Mampu menjelaskan mengenai
eicosanoid
Overview of
fatty acid
metabolism
showing the
major
pathways
and end
products
Lipogenesis
• Location : cytoplasm.
• Cofactor requirements include NADPH,ATP,
Mn2+, biotin, HCO3, acetyl CoA.
• Acetyl CoA is the immediate substrate.
• Free palmitate is the end product.
• Initial reaction : carboxylation of acetyl CoA
to malonyl CoA by ATP and acetyl CoA
carboxylase .
• Acetyl CoA carboxylase has a requirement
for the vitamin biotin
Lipogenesis = Fatty acid synthesis
occurs primarily in the cytoplasm
of these tissues:
• Liver
• Adipose (fat)
• Central Nervous System
• Lactating mammary gland
Remember:
Glucagon and epinephrine
inhibit fatty acid synthesis,
and insulin stimulates it
The fatty acid synthesis may be learnt in 3
stages
• I. Production of acetyl CoA and NADPH
• II. Conversion of acetyl CoA to malonyl
CoA
• III. Reactions of fatty acid synthase
complex.
I. Production of acetyl CoA and
NADPH
• Acetyl CoA is produced in the mitochondria by the
oxidation of pyruvate and fatty acids, degradation of
carbon skeleton of certain amino acids, and from
ketone bodies.
• Mitochondria, not permeable to acetyl CoA.
• Acetyl CoA condenses with oxaloacetate in
mitochondria to form citrate.
• The transport of acetyl CoA from mitochondria to
cytosol is coupled with the cytosomal production of
NADPH and CO2 which is highly advantageous to the
cell for optimum synthesis of fatty acids.
II. Conversion of acetyl CoA to malonyl CoA
• Malonyl-CoA is formed from acetyl-CoA by a
carboxylation reaction that requires biotin and ATP.
• The enzyme is acetyl-CoA carboxylase, a regulatory
enzyme that is inhibited by phosphorylation, activated
by dephosphorylation and by citrate, and induced by
insulin.
• The enzyme that phosphorylates acetyl-CoA
carboxylase is the AMP-activated protein kinase (not
protein kinase A).
• Enzyme acetyl CoA carboxylase is an ATP-
dependent reaction and requires biotin for CO2
fixation.
III. Reactions of fatty acid
synthase complex
• Step 1: Carboxylation of Acetyl CoA
• Step 2: Three C and Two C Units
are Added
• Step 3: Condensation
• Step 4: Reduction
• Step 5: Dehydration
• Step 6: Second Reduction
• Cycling of Reactions (7 times)
• Step 7: Palmitic acid is Released
• 1 Acetyl CoA +7 Malonyl CoA +14
NADPH +14 H+ → 1 Palmitate + 7
CO2 +14 NADP+ + 8 CoA+ 6 H2O
Fatty Acid Synthase Complex
• The Fatty Acid Synthase
Complex Is a Homodimer of Two
Polypeptide Chains Containing
Six Enzyme Activities and the
Acyl Carrier Protein
C16
The acyl group is now ready to condense
with a new malonyl group to repeat the process.
thioesterase
palmitoyl-ACP + H2O palmitate + ACP-SH
separate elongation
and/or unsaturation