570
15 Lipids
Acetyl-GoA
Malonyl-GoA
~
Palmitate
'~I _ _ _ / II
Malonyl-GoA
III
TE ......". Palmitate
\
Acetyl-GoA
Fig.15.4. The fatty acid
synthase complex of the
chicken is a dimer of two
identical, oppositely orientated (head-to-tail) subunits.
The seven enzyme functions
and the acyl-binding protein
function (ACP) are distributed amongst three domains:
domain I (elongation) of each
subunit interacts functionally
with domains II (reduction)
and III (paLmitate release) of
the other subunits [264].
AT, Acetyl transacylase;
MT, malonyl transacylase;
KS, ~-ketoacyl synthase;
KR, ~-ketoacyl reductase;
DR, dehydratase; ER, enoyl
reductase; TE, thioesterase;
ACp, acyl carrier protein
different FAS subdomains of chicken and yeast it
is 14-31 % [36]. The polypeptide chain is subdivided into three domains (Fig. 15.4). Domain I
(127 kDa) includes the activities of ~-ketoacyl
synthase (KS) and the acetyl and malonyl transacylases (AT and MT). This is the attachment
point for the primer and elongation substrate, and
is responsible for the elongation reactions.
Domain II (107 kDa) includes the ~-ketoacyl and
enoyl reductases (KR and ER), the dehydratase
(D H) and ACP; the acyl residue remains bound to
ACP during the reduction reactions on this
domain. Binding is via the same 4' -phosphopantetheine structure found in CoA (Fig. 15.5).
When the growing chain reaches a length of
16-18 C atoms, it is released by the thioesterase
activity (TE) localized on domain III (33 kDa).
The two subunits are arranged head-to-tail such
that the pantetheine SH of one subunit lies opposite the cysteine SH of KS on the other subunit.
Thus, the functional unit of fatty acid biosynthesis
is composed of domain I of one subunit and
domains II and III of the other subunit [264]. Dissociation to monomers inactivates the whole reaction but this is reversible [195, 246]. Immunological comparisons show that FASs from liver, milk
gland and fat tissues of the same species are identical, that the FASs of different mammals are partiAsp;
OH
CH3
OH
:
1
:
1
1
I
:
Ser--<-O-P-O-CH -C----CH-G-NH-CH -CH -G-+-NH-CH -CH -SH
1
:
II
2 1
II
2
2 II:
2
2
Leu l 0
CH3
0
0 l
I
I
I
I
I
I
I
I
I
I
I
I
OH
OH
CH
OH
:
I;
1
1 3
1
:
Adenine H 2 C- O-P +O-P-O-CH2-C----CH-C- NH-CH2-CH 2-C+NH-CH2-CH2-SH
~
11:11
1
II
II:
o
0 l 0
CH3
0
0 l
:
1
H H H H
:
:
: •
4'·Phosphopantothenic acid
... :
HO
0
:
:
I
:
I
O=P-OH
:
1
: ..
4'-Phosphopantetheine-----------OH
i ,
Fig.15.5. The acyl-binding proteins (ACP) of fatty acid synthase (above) and CoA (below) contain the same 4'phosphopantetheine structure [195]
15 Lipids
Acetyl-GoA
Malonyl-GoA
~
Palmitate
'~I _ _ _ / II
Malonyl-GoA
III
TE ......". Palmitate
\
Acetyl-GoA
Fig.15.4. The fatty acid
synthase complex of the
chicken is a dimer of two
identical, oppositely orientated (head-to-tail) subunits.
The seven enzyme functions
and the acyl-binding protein
function (ACP) are distributed amongst three domains:
domain I (elongation) of each
subunit interacts functionally
with domains II (reduction)
and III (paLmitate release) of
the other subunits [264].
AT, Acetyl transacylase;
MT, malonyl transacylase;
KS, ~-ketoacyl synthase;
KR, ~-ketoacyl reductase;
DR, dehydratase; ER, enoyl
reductase; TE, thioesterase;
ACp, acyl carrier protein
different FAS subdomains of chicken and yeast it
is 14-31 % [36]. The polypeptide chain is subdivided into three domains (Fig. 15.4). Domain I
(127 kDa) includes the activities of ~-ketoacyl
synthase (KS) and the acetyl and malonyl transacylases (AT and MT). This is the attachment
point for the primer and elongation substrate, and
is responsible for the elongation reactions.
Domain II (107 kDa) includes the ~-ketoacyl and
enoyl reductases (KR and ER), the dehydratase
(D H) and ACP; the acyl residue remains bound to
ACP during the reduction reactions on this
domain. Binding is via the same 4' -phosphopantetheine structure found in CoA (Fig. 15.5).
When the growing chain reaches a length of
16-18 C atoms, it is released by the thioesterase
activity (TE) localized on domain III (33 kDa).
The two subunits are arranged head-to-tail such
that the pantetheine SH of one subunit lies opposite the cysteine SH of KS on the other subunit.
Thus, the functional unit of fatty acid biosynthesis
is composed of domain I of one subunit and
domains II and III of the other subunit [264]. Dissociation to monomers inactivates the whole reaction but this is reversible [195, 246]. Immunological comparisons show that FASs from liver, milk
gland and fat tissues of the same species are identical, that the FASs of different mammals are partiAsp;
OH
CH3
OH
:
1
:
1
1
I
:
Ser--<-O-P-O-CH -C----CH-G-NH-CH -CH -G-+-NH-CH -CH -SH
1
:
II
2 1
II
2
2 II:
2
2
Leu l 0
CH3
0
0 l
I
I
I
I
I
I
I
I
I
I
I
I
OH
OH
CH
OH
:
I;
1
1 3
1
:
Adenine H 2 C- O-P +O-P-O-CH2-C----CH-C- NH-CH2-CH 2-C+NH-CH2-CH2-SH
~
11:11
1
II
II:
o
0 l 0
CH3
0
0 l
:
1
H H H H
:
:
: •
4'·Phosphopantothenic acid
... :
HO
0
:
:
I
:
I
O=P-OH
:
1
: ..
4'-Phosphopantetheine-----------OH
i ,
Fig.15.5. The acyl-binding proteins (ACP) of fatty acid synthase (above) and CoA (below) contain the same 4'phosphopantetheine structure [195]