2. INTRODUCTION
Biological lipids are a chemically diverse group of compounds,
the common and defining feature is their insolubility in water.
Known as fats and oils
Hydrophobic and soluble in ethanol like alcohol, petroleum and
chloroform
Classified into 2 general types
Fats and waxes (can be hydrolyzed with ester linkages)
cholesterol and steroids (cannot be hydrolyzed)
3. The simplest lipids are the fatty acids, which rarely exist alone in
nature, but instead are usually a component of more complex lipids.
Fatty acids are carboxylic acids with a long hydrocarbon chain
attached.
They are amphiphatic in nature.
Although the acid end is polar, the nonpolar hydrocarbon tail makes
fatty acids insoluble (or sparingly soluble) in water.
Fatty acids can be classified by how many double bonds are present
in the hydrocarbon tail:
- Saturated fatty acids have only single bonds
- Monounsaturated fatty acids have one double bond
- Polyunsaturated fatty acids have two or more double
bonds
4. Biological Functions
• Storage of energy
• Constituents of cellular membranes
• Anchors for membrane proteins
• Cofactors for enzymes
• Signaling molecules
• Pigments
• Detergents
• Transporters
• Antioxidants
5. Catabolism and Anabolism
• Catabolism of fatty acids
– produced acetyl-CoA
– reducing power to NADH
– location: mitochondria
• Anabolism of fatty acids
– requires malonyl-CoA and acetyl-CoA
– reducing power from NADPH
– location: cytosol in animals, chloroplast in plants
6. Overview of Fatty Acid Synthesis
• Biosyntesis requires a
3C intermediate called
malonyl-CoA
• It is formed from
acetyal –CoA and
bicarbonate
• This reaction is
catalyzed by acetyal-
CoA carbooxylase
7. Synthesis of Malonyl-CoA
• The three-carbon precursor for fatty
acid synthesis is made from acetyl-
CoA and CO2
• The reaction is catalyzed by acetyl-
CoA carboxylase (ACC)
• ACC is a bifunctional enzyme
– Biotin carboxylase
– Transcarboxylase
• ACC contains biotin, nature’s carrier
of CO2
– Biotin shuttles between the two active
sites
8. Fatty Acid Synthesis
• Overall goal is to attach a two-carbon acetate unit from
malonyl-CoA to a growing chain and then reduce it
• Reaction involves cycles of four enzyme-catalyzed steps
– Condensation of the growing chain with activated acetate
– Reduction of carbonyl to hydroxyl
– Dehydration of alcohol to trans-alkene
– Reduction of alkene to alkane
• The growing chain is initially attached to the enzyme via
a thioester linkage
• During condensation, the growing chain is transferred to
the acyl carrier protein
• After the second reduction step, the elongated chain is
transferred back to fatty acid synthase
9. Acyl Carrier Protein
• Contains a covalently attached
prothetic group 4’-phospho-
pantethiene
• The acyl carrier protein delivers
acetate (in the first step) or
malonate (in all the next steps) to
the fatty acid synthase
• The acyl carrier protein shuttles the
growing chain from one active site
to another during the four-step
reaction
10. Charging the Acyl Carrier Protein
and Fatty Acid Synthase
• Two thiols participate in the fatty acid synthesis
– Thiol from 4-phosphopantethine in acyl carrier protein
– Thiol from cysteine in fatty acid synthase
• Both thiols must be charged for the condensation
reaction to occur
– In the first step, acetyl from acetyl-CoA is transferred to
acyl carrier protein
– Acyl carrier protein passes this acetate to fatty acid
synthase
– Acyl carrier protein is then re-charged with malonyl
from malonyl-CoA
17. • The mitochondrial inner membrane is impermeable to
acetyl-CoA, so an indirect shuttle transfers acetyl group
equivalents across the inner membrane .
• Intramitochondrial acetyl-CoA first reacts with oxaloacetate
to form citrate, with the help of citrate synthase enzyme.
• Citrate then passes through citrate transporter present in
inner membrane to cytosol which further citrate convert into
acetyl-CoA and oxaloacetate by citrate lyase in an ATP-
dependent reaction.
• Oxaloacetate cannot return to the mitochondrial matrix
directly, then cytosolic malate dehydrogenase reduces the
oxaloacetate to malate and malate return to mitochondrial
membrane by the alpha-ketoglutarate transporter.
• In the matrix, malate is reoxidized to oxaloacetate to
complete the shuttle.
• Then oxaloacetate back to convert citrate.
19. • The reaction catalyzed by acetyl-coA carboxylase is the rate
limiting-step in the biosynthesis of fatty acid.
• Palmitoyl-CoA is a feedback inhibitor of the enzyme; citrate is
an allosteric activator.
• Acetyl-CoA carboxylase is also regulated by covalent
modification. Phosphorylation, triggered by the hormones
glucagon and epinephrine, inactivates the enzyme and
reduces its sensitivity to activation by citrate there by slowing
fatty acid synthesis.
20. Route of synthesis of
other Fatty Acids
• Animals can readily introduce
one double bond to palmitate
and stearate
• Vertebrates cannot introduce
additional double bonds between
C10 and methyl-terminal
• We must obtain linoleate and -
linolenate with diet; these are
essential fatty acids
• Plants, algae, and some insects
synthesize linoleate from oleate
21. Desaturation of fatty acid
• The double bond is introduced into fatty
acid chain by an oxidative reaction is
catalyzed by fatty acyl-CoA
desaturase,a mixed- function oxidase
• Two different substrates, the fatty acid
and NADH or NADPH, simultaneously
undergo two electron oxidations
22. Reference
• Lehninger A.L.,Nelson D.L.,Principles of Biochemist
ry,M.M.Cox.Worth Publishing.
• Moat A.G., Foster J W., Spector M P.
Microbial Physiology,4th edition.
