Chapter 24Fatty AcidSynthesis (Stage 3:FA SynthesisFirst Cycle…
Transportation of acetyl-CoA
Acetyl-CoA transported from
the mitochondria to the cytosol.
Acetyl-CoA can not pass through the membranes of the mitochondria.
Acetyl-CoA combines with oxaloacetate to form citrate in order to
pass through the mitochondrial membranes.
, ATP-citrate lyase uses ATP to
separate citrate → oxaloacetate + acetyl-CoA
Returns to the cytosol as either
pyruvate or malate
→ Malate + NAD+
Malate + NADP+ → pyruvate + NADPH + CO2
Elongation cycle begins with introduction to a acyl carrier protein (ACP).
, a domain within the FAS I enzyme complex,
of malonyl-CoA to ACP;
:!: forms malonyl-ACP
Fatty Acid Synthase I
The enzyme complex that facilitates lipigenesis
Decarboxylation drives condensation of Acetyl-CoA and Malonyl-CoA
β-ketoacetyl-ACP synthase (KS)
Goes through MAT → malonyl-ACP
:star:Malonyl-ACP looses CO2 and condenses with acetyl-KSase
Goes through MAT → acetyl-ACP
Attaches to KS at serine of ACP; ACP is released
Acetoacetyl-ACP's β-carbonyl is reduced
β-ketoacyl-ACP reductase (KR)
β-Hydroxyacyl-ACP dehydrogenase removes a water from between the α- & β-C.
β-Hydroxyacyl-ACP dehydratase (DH)
Ruduction of the double bond between the α- and β-C.
β-Enoyl-ACP reductase (ER)
Carboxylation of acetyle-CoA
:warning: The committed step
FA are made from acetate, however, acetate must be
activated in order to play its part.
acetyl-CoA + HCO3- + ATP →
+ ADP + P + H+
Acetyl-CoA carboxylase is biotin dependent
Step 1 of the reaction:
ATP phosphorylates HCO3-
Biotin is then carboxylated on one of it's NH groups
Step 2 of the reaction:
Biotin pendulates from the (now) Pi to acetyl-CoA
Biotin carboxylates acetyl-CoA and forms
Acetyl-CoA Carboxylase contains three subunits
Biotin carboxyl carrier protein
Where biotin is attached
Where the carboxyl group is transferred from biotin to Acetyl-CoA
Where biotin is carboxylized
Acetyl-CoA Carboxylase is covalently regulated through phosphorylation
acetyl-CoA carboxylase binds to citrate with high affinity, thus,
is :check: activated at low citrate concentrations.
High concentrations of pamitoyl-CoA :red_cross:
acetyl-CoA carboxylase is :check: activated by
high concentrations of citrate
concentrations of fatty acyl-CoA will :red_cross:
KS combines a malonyl-ACP to the butyryl-ACP making β-ketoacyl-ACP
KR reduces β-ketoacyl-ACP to make β-hydroxyacyl-ACP using NADPH
DH dehydrates β-hydroxyacyl-ACP to β-enoyl-ACP
ER reduces β-enoyl-ACP to acyl(Cn+2)-ACP using NADPH
Malonyl-CoA :red_cross: carnitine acyltransferase; :red_cross: β-oxidation
Citrate :check: acetyl-CoA carboxylase
Fatty acyl-CoA :red_cross: acetyl-CoA carboxylase
Glucagon :check: lipases | :red_cross: ACC
Insulin :red_cross: lipases | :check: ACC
:warning: Instead of a CoA it should be ACP in this reaction