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Fatty Acids Biosynthesis
• Arachidonic acid is referred to as an ω-6 fatty
acid because the closest double bond to the
end begins six carbons from ω end.
• Linoleic acid, is the precursor of arachidonic
acid, the substrate for prostaglandin synthesis
• linolenic acid, the precursor of other ω -3
fatty acids important for growth and
development
SYNTHESIS OF FATTY ACIDS
• FA are mainly supplied by diet
• Excessive carbohydrates and proteins are
converted to FA which are stored as TAG
• In humans, fatty acid synthesis occurs
– primarily in the liver and lactating mammary glands
– To a lesser extent in adipose tissues
• The process incorporates carbons from acetyl
CoA into the growing fatty acid chain, using ATP
and NADPH
Production of cytosolic acetyl CoA
• 1st step Transfer of acetate units from
mitochondrial acetyl-CoA to the cytosol
• The coenzyme A portion of acetyl-CoA cannot
cross the mitochondrial membrane; only the
acetyl portion is transported to the cytosol.
• Citrate is produced by the condensation of
oxaloacetate (OAA) and acetyl CoA.
Carboxylation of acetyl CoA to form
malonyl CoA
• The energy for the carbon-to- carbon
condensations in fatty acid synthesis is
supplied by the process of carboxylation and
then decarboxylation of acetyl groups in the
cytosol.
Formation of malonyl-CoA
• Irreversible process
• Catalyzed by acetyl-CoA
carboxylase.
• The bacterial enzyme has three
separate polypeptide subunits
• In animal cells, all three activities
are part of a single multifunctional
polypeptide.
• In all cases, the enzyme contains a
biotin prosthetic group
• In all organisms, the long carbon chains of fatty acids are assembled
in a repeating four-step sequence, catalyzed by a system collectively
referred to as fatty acid synthase.
• There are two major variants of fatty acid synthase:
– fatty acid synthase I (FAS I), found in vertebrates and fungi,
– fatty acid synthase II (FAS II), found in plants and bacteria.
• The FAS I is a single multifunctional polypeptide chain (Mr 240,000).
• The mammalian FAS I is the prototype.
• Seven active sites for different reactions lie in separate domains.
• The mammalian polypeptide functions as a homodimer (Mr
480,000).
• The subunits appear to function independently.
Fatty acids elongation
• Long-Chain Saturated Fatty Acids Are Synthesized from
Palmitate
• fatty acid elongation systems present in the smooth
endoplasmic reticulum and in mitochondria
• Different enzyme systems are involved, and coenzyme A
rather than ACP is the acyl carrier in the reaction, the
mechanism of elongation in the ER is otherwise identical
to that in palmitate synthesis:
• The double bond is introduced into the fatty acid chain
by an oxidative reaction catalyzed by fatty acyl–CoA
desaturase, a mixed-function oxidase
Fatty Acid Biosynthesis Is Tightly Regulated
• The reaction catalyzed by acetyl-CoA carboxylase is the rate-
limiting step in the biosynthesis of fatty acids, and this
enzyme is an important site of regulation.
• In vertebrates, palmitoyl-CoA, the principal product of fatty
acid synthesis, is a feedback inhibitor of the enzyme;
• citrate is an allosteric activator
• When the concentrations of mitochondrial
acetyl-CoA and ATP increase, citrate is
transported out of mitochondria.
• it then becomes both the precursor of
cytosolic acetyl-CoA and an allosteric signal for
the activation of acetyl-CoA carboxylase
• citrate inhibits the activity of
phosphofructokinase-1, reducing the flow of
carbon through glycolysis.
• 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, thereby slowing fatty acid synthesis.
• In its active form, acetyl-CoA carboxylase
polymerizes into long filaments phosphorylation
is accompanied by dissociation into monomeric
subunits and loss of activity.
• when animals ingest an excess of certain
polyunsaturated fatty acids, the expression of
genes encoding a wide range of lipogenic
enzymes in the liver is suppressed.
• Β-oxidation is blocked by malonyl-CoA, which
inhibits carnitine acyltransferase-I
Fatty  Acids synthesisand imporatnce.pptx
Fatty  Acids synthesisand imporatnce.pptx

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Fatty Acids synthesisand imporatnce.pptx

  • 2.
  • 3. • Arachidonic acid is referred to as an ω-6 fatty acid because the closest double bond to the end begins six carbons from ω end. • Linoleic acid, is the precursor of arachidonic acid, the substrate for prostaglandin synthesis • linolenic acid, the precursor of other ω -3 fatty acids important for growth and development
  • 4.
  • 5. SYNTHESIS OF FATTY ACIDS • FA are mainly supplied by diet • Excessive carbohydrates and proteins are converted to FA which are stored as TAG • In humans, fatty acid synthesis occurs – primarily in the liver and lactating mammary glands – To a lesser extent in adipose tissues • The process incorporates carbons from acetyl CoA into the growing fatty acid chain, using ATP and NADPH
  • 6.
  • 7. Production of cytosolic acetyl CoA • 1st step Transfer of acetate units from mitochondrial acetyl-CoA to the cytosol • The coenzyme A portion of acetyl-CoA cannot cross the mitochondrial membrane; only the acetyl portion is transported to the cytosol. • Citrate is produced by the condensation of oxaloacetate (OAA) and acetyl CoA.
  • 8.
  • 9.
  • 10. Carboxylation of acetyl CoA to form malonyl CoA • The energy for the carbon-to- carbon condensations in fatty acid synthesis is supplied by the process of carboxylation and then decarboxylation of acetyl groups in the cytosol.
  • 11.
  • 12. Formation of malonyl-CoA • Irreversible process • Catalyzed by acetyl-CoA carboxylase. • The bacterial enzyme has three separate polypeptide subunits • In animal cells, all three activities are part of a single multifunctional polypeptide. • In all cases, the enzyme contains a biotin prosthetic group
  • 13. • In all organisms, the long carbon chains of fatty acids are assembled in a repeating four-step sequence, catalyzed by a system collectively referred to as fatty acid synthase. • There are two major variants of fatty acid synthase: – fatty acid synthase I (FAS I), found in vertebrates and fungi, – fatty acid synthase II (FAS II), found in plants and bacteria. • The FAS I is a single multifunctional polypeptide chain (Mr 240,000). • The mammalian FAS I is the prototype. • Seven active sites for different reactions lie in separate domains. • The mammalian polypeptide functions as a homodimer (Mr 480,000). • The subunits appear to function independently.
  • 14.
  • 15.
  • 16. Fatty acids elongation • Long-Chain Saturated Fatty Acids Are Synthesized from Palmitate • fatty acid elongation systems present in the smooth endoplasmic reticulum and in mitochondria • Different enzyme systems are involved, and coenzyme A rather than ACP is the acyl carrier in the reaction, the mechanism of elongation in the ER is otherwise identical to that in palmitate synthesis: • The double bond is introduced into the fatty acid chain by an oxidative reaction catalyzed by fatty acyl–CoA desaturase, a mixed-function oxidase
  • 17.
  • 18. Fatty Acid Biosynthesis Is Tightly Regulated • The reaction catalyzed by acetyl-CoA carboxylase is the rate- limiting step in the biosynthesis of fatty acids, and this enzyme is an important site of regulation. • In vertebrates, palmitoyl-CoA, the principal product of fatty acid synthesis, is a feedback inhibitor of the enzyme; • citrate is an allosteric activator
  • 19. • When the concentrations of mitochondrial acetyl-CoA and ATP increase, citrate is transported out of mitochondria. • it then becomes both the precursor of cytosolic acetyl-CoA and an allosteric signal for the activation of acetyl-CoA carboxylase • citrate inhibits the activity of phosphofructokinase-1, reducing the flow of carbon through glycolysis.
  • 20. • 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, thereby slowing fatty acid synthesis. • In its active form, acetyl-CoA carboxylase polymerizes into long filaments phosphorylation is accompanied by dissociation into monomeric subunits and loss of activity.
  • 21. • when animals ingest an excess of certain polyunsaturated fatty acids, the expression of genes encoding a wide range of lipogenic enzymes in the liver is suppressed. • Β-oxidation is blocked by malonyl-CoA, which inhibits carnitine acyltransferase-I