untitled
TRANSCRIPT
-
Fatty
Aci
d Sy
nthe
sis
-
Co
mpa
riso
n o
f fa
tty
aci
d bi
osy
nth
esis
an
d de
gra
datio
n
-
Site
s o
f reg
ula
tion
o
f fa
tty
aci
d m
eta
bolis
m
-
The
form
atio
n o
f ma
lon
yl~
Co
A is
the
com
mitt
ed st
ep in
fa
tty
aci
d sy
nth
esis
Irrev
ersib
le re
actio
n ca
taly
zed
by ac
etyl
Co
A ca
rbo
xyl
ase
(ACC
):
acet
yl~
CoA
+
AT
P +
H
CO3-
mal
on
yl~
CoA
+ A
DP
+ Pi
+
H
+
ACC
co
nta
ins
a bi
otin
pr
ost
hetic
gr
ou
p, an
d th
e re
actio
n m
echa
nism
is
simila
r to
pyru
vat
e ca
rbo
xyl
ase
and
pro
pio
nyl
~Co
A ca
rbo
xyl
ase
reac
tion
s.
The
two
st
eps
in th
e re
actio
n:
Bio
tin----En
zym
e +
AT
P +
H
CO3-
CO
2-B
iotin
----En
zym
e +
A
DP
+ Pi
CO2-
Bio
tin----En
zym
e +
ac
etyl
~Co
A m
alo
nyl
~Co
A +
B
iotin
----En
zym
e
No
tes:
In
E.
co
li, 3
subu
nits
: bi
otin
ca
rbo
xyl
ase,
tr
ansc
arbo
xyl
ase,
bi
otin
-ca
rbo
xyl
ca
rrie
r pr
ote
in.
In bi
rds
and
mam
mal
s a
singl
e po
lype
ptid
e ch
ain
ha
s al
l thr
ee fu
nct
ion
s.
ACC
is
subje
ct to
ho
rmo
nal
re
gula
tion
. D
epho
spho
ryla
ted
form
is
activ
e, ph
osp
hory
late
d fo
rm is
less
ac
tive.
G
luca
gon
an
d ep
inep
hrin
e st
imu
late
ph
osp
hory
latio
n, In
sulin
st
imu
late
s de
pho
spho
ryla
tion
.
Citr
ate
activ
ates
an
d pa
lmito
yl~
CoA
inhi
bits
th
e en
zym
e
Pho
spho
ryla
tion
le
ads
to de
poly
mer
izat
ion
.
-
ATP-
depe
nde
nt c
arb
oxy
latio
n pr
ovi
des
en
erg
y in
put.
The
CO2
is lo
st la
ter
durin
g co
nde
nsa
tion
w
ith th
e
gro
win
g fa
tty a
cid.
The
sp
on
tan
eo
us
deca
rbo
xyla
tion
dr
ive
s th
e
con
den
satio
n re
act
ion
.
H 3C
CSC
oA
O CH2
CSC
oA
O
OO
Cace
tyl-C
oA
mal
onyl
-Co
A
The
in
put t
o fa
tty a
cid
syn
the
sis
is ac
etyl
-
CoA
, w
hich
is
carb
oxy
late
d to
mal
on
yl-Co
A.
-
As w
ith oth
er
carb
oxy
latio
n re
act
ions,
th
e enzy
me pr
ost
hetic
gr
oup
is b
iotin
.
ATP-
depe
nde
nt c
arb
oxy
latio
n of t
he bi
otin
, ca
rrie
d out a
t one act
ive si
te 1
, is
follo
wed
by tr
ansf
er
of t
he ca
rboxy
l gr
oup
to ace
tyl-C
oA
at a
se
cond
act
ive si
te 2
.
Ace
tyl-C
oA
Carb
oxyl
ase
cata
lyzes
the
2-st
epre
act
ion
by w
hich
ace
tyl-
CoA
is
carb
oxy
late
d to
form
m
alo
nyl
-
CoA
.
ll
En
zym
e-bi
otin
HCO
3- +
AT
P
ADP
+ P i
En
zym
e-bi
otin
-CO
2-
O
CH
3-C-
SCo
A a
cety
l-Co
A O
-
O2C
-CH
2-C-
SCo
A m
alo
nyl-
CoA
llEn
zym
e-bi
otin
1 2
-
The
o
vera
ll re
act
ion
, w
hich
is
sp
on
tan
eou
s, m
ay
be
sum
ma
rize
d a
s:
HCO
3+
ATP
+ ac
etyl
-Co
A
AD
P+
P i
+ m
alo
nyl
-
CoA
ll
En
zym
e-bi
otin
HCO
3- +
AT
P
ADP
+ P i
En
zym
e-bi
otin
-CO
2-
O
CH
3-C-
SCo
A a
cety
l-Co
A O
-
O2C
-CH
2-C-
SCo
A m
alo
nyl-
CoA
llEn
zym
e-bi
otin
1 2
-
Bio
tin is
linke
d to
th
e enzy
me by
an am
ide bo
nd
betw
een
the te
rmin
al c
arb
oxy
l of t
he bi
otin
si
de ch
ain
and
the -
am
ino gr
oup
of a
ly
sin
ere
sidu
e.
The co
mbi
ned
biotin
and
lysin
e si
de ch
ain
s act
as
a lo
ng
flexib
le ar
mth
at a
llow
s th
e bi
otin
rin
g to
tra
nsl
oca
te
betw
een th
e 2
act
ive si
tes.
CHCH
H 2C
SCHN
HC
N
O
(CH
2) 4C
NH(C
H2) 4
CHCO
NH
O
COO
Carb
ox
ybio
tin
lysin
e re
sidu
e
-
Ace
tyl-C
oA
Ca
rbo
xyl
ase,
w
hich
co
nve
rts a
cety
l-CoA
to
malo
nyl-
CoA,
is
the co
mm
itted
st
epof t
he fa
tty a
cid
synt
hesi
s pa
thw
ay.
The m
am
malia
n enzy
me is
reg
ula
ted,
by
phosp
hory
latio
n
allo
steric
contro
l by
loca
l meta
bolit
es.
Con
form
atio
nal
ch
ange
sass
oci
ate
d w
ith re
gula
tion:
In
th
e ac
tive
confo
rmatio
n, Ac
ety
l-CoA
Carb
oxy
lase
ass
oci
ate
s to
fo
rm m
ulti
meric
fila
men
tou
sco
mpl
exe
s.
Tr
ansi
tion to
th
e in
activ
eco
nfo
rmatio
n is
ass
oci
ate
d w
ith
diss
oci
atio
n to
yie
ld th
em
on
om
eric
form
o
f the
en
zym
e (pr
oto
me
r).
-
The de
crea
sed
produ
ctio
n of m
alo
nyl
-Co
Apr
eve
nts
energ
y-util
izin
g fa
tty a
cid
synt
hesi
s w
hen ce
llula
r energ
y st
ore
s are
depl
ete
d. (A
MP
is a
bunda
nt o
nly
whe
n AT
P ha
s be
en
ext
ensi
vely
deph
osp
hory
late
d.)
AM
P-A
ctiv
ate
d K
ina
seca
taly
zes
pho
spho
ryla
tion
of A
cety
l-Co
A Ca
rbo
xyl
ase,
cau
sing
inhi
bitio
n.
Ph
osp
hory
late
d pr
oto
mer
of
A
cety
l-CoA
Ca
rbo
xyl
ase
(inac
tive)
D
epho
spho
ryla
ted
Poly
mer
o
f A
cety
l-CoA
Ca
rbox
ylas
e (ac
tive)
Citr
ate
Dep
hosp
hory
late
d,
e.g.
, by
in
sulin
-
activ
ated
Pr
ote
in
Pho
spha
tase
Palm
itoyl
-Co
A
Pho
spho
ryla
ted,
e.
g., via
AM
P-ac
tivat
ed K
inas
e w
hen ce
llula
r st
ress
o
r
exer
cise
de
plet
es A
TP.
Reg
ula
tion
of A
cety
l-CoA
C
arb
oxyl
ase
-
Whe
n AM
P is
hig
h (A
TP lo
w), m
alo
nyl-
CoA
produ
ctio
n is
di
min
ishe
d, re
leasi
ng
fatty
aci
d oxid
atio
n fro
m in
hibi
tion. Th
is
will
lead
to in
crea
sed
ATP
pr
odu
ctio
n.
AM
P-A
ctiv
ated
K
inas
eha
s a si
gnific
ant r
ole
eve
n in
tissu
es
(e.g.
, ca
rdia
c m
usc
le) th
at d
o not
sign
ificantly
syn
thesi
ze fa
tty
aci
ds.
In su
ch tis
sues
mal
on
yl-
CoA
, pr
odu
ced
via one
isofo
rm of A
cety
l-CoA
Carb
oxy
lase
, fu
nct
ions
main
ly as
an
inhi
bito
rof
fatty
ac
id o
xid
atio
n.
H3C
CSC
oA
O CH2
CSC
oA
O
OO
C
acet
yl-Co
A
mal
onyl
-Co
A
ATP
+
H
CO3
A
DP
+ P i
Ace
tyl-C
oA
Carb
oxyl
ase
(inhi
bite
d by
AM
P-A
ctiv
ated
Kin
ase)
-
A cA
MP
casc
ade
, a
ctiv
ate
d by
gl
uca
gon
&
epi
ne
phrin
e w
hen
bl
oo
d gl
uco
se is
lo
w, m
ay
als
o
resu
lt in
ph
osp
hory
latio
n o
f Ace
tyl-C
oA
Carb
oxy
lase
via
cAM
P-D
epen
den
t Pro
tein
K
inas
e.
With
Ac
ety
l-Co
A Ca
rbo
xyla
se in
hibi
ted,
a
cety
l-Co
A re
ma
ins
ava
ilabl
e fo
r sy
nth
esi
s o
f ke
ton
e bo
die
s, th
e
alte
rna
tive
m
eta
bolic
fu
el u
sed
whe
n bl
oo
d gl
uco
se
is lo
w.
H3C
CSC
oA
O CH2
CSC
oA
O
OO
Cace
tyl-C
oA
mal
onyl
-Co
A
-
The
a
nta
gon
istic
e
ffect
o
f in
sulin
, pr
odu
ced
whe
n
blo
od
glu
cose
is
hi
gh, is
a
ttrib
ute
d to
a
ctiv
atio
n o
f Pr
ote
in Ph
osp
hata
se.
Ph
osp
hory
late
d pr
oto
mer
of
A
cety
l-Co
A Ca
rbo
xyl
ase
(inac
tive)
D
epho
spho
ryla
ted
Poly
mer
o
f A
cety
l-Co
A Ca
rbox
ylas
e ( ac
tive)
Citr
ate
Dep
hosp
hory
late
d,
e.g.
, by
in
sulin
-
activ
ated
Pr
ote
in
Pho
spha
tase
Palm
itoyl
-Co
A
Pho
spho
ryla
ted,
e.
g., via
AM
P-ac
tivat
ed K
inas
e w
hen ce
llula
r st
ress
o
r
exer
cise
de
plet
es A
TP.
Reg
ula
tion
of
A
cety
l-Co
A C
arb
oxyl
ase
-
Palm
itoyl
-Co
A(pr
odu
ct of F
atty
Aci
d Sy
ntha
se) p
rom
ote
s th
e
inac
tive
confo
rmatio
n, di
min
ishi
ng
produ
ctio
n of m
alo
nyl-
CoA,
the pr
ecu
rsor
of f
atty
aci
d sy
nthe
sis.
This
is a
n exa
mpl
e of f
eedb
ack
inhi
bitio
n.
Reg
ula
tion
of
Ace
tyl-C
oA
Carb
ox
ylas
e by
loca
l met
abo
lites
:
Ph
osp
hory
late
d pr
oto
mer
of
A
cety
l-CoA
Ca
rbo
xyl
ase
(inac
tive)
D
epho
spho
ryla
ted
Poly
mer
of
A
cety
l-CoA
Ca
rboxyl
ase
(activ
e)
Citr
ate
Dep
hosp
hory
late
d,
e.g.
, by
in
sulin
-
activ
ated
Pr
ote
in
Pho
spha
tase
Palm
itoyl
-Co
A
Pho
spho
ryla
ted,
e.
g., via
AM
P-ac
tivat
ed K
inas
e w
hen ce
llula
r st
ress
o
r
exer
cise
de
plet
es A
TP.
Reg
ula
tion
of A
cety
l-Co
A C
arb
oxyl
ase
-
[Citr
ate
] is hi
gh w
hen
th
ere
is
a
dequ
ate
a
cety
l-Co
A e
nte
ring
Kre
bs Cy
cle
.
Exce
ss a
cety
l-Co
A is
th
en
co
nve
rted
via
m
alo
nyl-
CoA
to fa
tty a
cids
fo
r st
ora
ge.
G
luco
se-6-
phosp
hata
se
gl
uco
se-6-
P gl
uco
se
G
luco
neo
genes
is G
lyco
lysis
py
ruvat
e fa
tty ac
ids
ac
etyl
Co
A ke
tone
bodi
es
ch
ole
ster
ol
ox
aloac
etat
e ci
trat
e
K
rebs
Cy
cle
Citr
ate
allo
steric
ally
ac
tivat
esAc
ety
l-Co
A Ca
rboxy
lase
.
-
Act
ive,
po
lym
eriz
ed
AC
C
ina
ctiv
e, de
poly
mer
ized
AC
Cci
tra
teph
osp
hory
l gro
up
AM
PK
pro
tein
ph
osp
hata
se 2A
oth
er in
sulin
-de
pen
den
t ph
osp
hata
se?
part
ially
po
lym
eriz
ed,
part
ially
a
ctiv
e
palm
itoyl
~C
oA
palm
itoyl
~C
oA
An
hy
poth
esis
for
the
regu
latio
n o
f AC
C
Ener
gy ch
arge
o
f cel
l co
ntr
ols
AM
PK.
Epin
ephr
ine
and
glu
cago
n ac
t by
cau
sing
inhi
bitio
n o
f PP2
AIn
sulin
ac
ts th
rou
gh u
nkn
ow
n ph
osp
hata
se
palm
itoyl
~Co
A di
sper
ses
filam
ents
pho
spho
ryla
tion
in
hibi
ts fo
rmat
ion
o
f fila
men
tsci
trat
e pr
om
ote
s po
lym
eriz
atio
n
-
Fatty
ac
id sy
nth
esi
sfro
m a
cety
l-Co
A &
ma
lon
yl-Co
A o
ccu
rs by
a
se
ries
of r
ea
ctio
ns
tha
t are
:
in
ba
cter
iaca
talyz
ed
by se
ven
se
para
te
en
zym
es.
in
m
amm
als
cata
lyze
d by
in
divi
dua
l do
ma
ins
of
a si
ngl
e la
rge
po
lype
ptid
e.
Evo
lutio
n o
f the
m
am
ma
lian
Fa
tty A
cid
Syn
thas
ea
ppa
ren
tly ha
s in
volv
ed
gen
e fu
sio
n.
NA
DPH
serv
es
as
elec
tro
n do
no
rin
tw
o re
act
ion
s in
volv
ing
subs
trate
re
duct
ion
.
The
N
ADPH
is
pr
odu
ced
ma
inly
by th
e Pe
nto
se
Pho
spha
te Pa
thw
ay.
-
Ma
mm
alia
n Fa
tty
Aci
d Sy
nth
ase
(F
AS)
keto
acyl
-A
CP sy
nth
ase
mal
on
yl/a
cety
l-Co
AA
CP tr
ansa
cyla
se
hydr
ox
yacy
l-ACP
de
hydr
atas
e
eno
yl-A
CP re
duct
ase
keto
acyl
-A
CP re
duct
ase
palm
itoyl
th
ioes
tera
se
Ma
mm
alia
n en
zym
e is
a ho
mo
dim
er o
f 272
kD
a su
bun
its
Mem
ber
of t
he m
ega
syn
tha
se fa
mily
.
In E.
co
li 7
diffe
ren
t en
zym
es +
A
CP
-
Fatty
Aci
dSy
ntha
se
prost
hetic
gro
ups
:
th
e th
iolo
f the
si
de-
chain
of a
cy
stei
ne
resi
due of C
onde
nsi
ng
Enzy
me do
main
.
th
e th
iolo
f ph
osp
hopa
nte
thei
ne,
equ
ivale
nt i
n st
ruct
ure
to
part
of c
oenzy
me A.
N
NNN
NH 2 O
OH
O
HH
H
CH2
H
OP
OP
OH 2
C
O
OO O
P O
O
O
CCCNHCH2
CH2
CNH
CH3
H 3C
HH
O
O
CH2
CH2
SH
O-m
erca
ptoet
hyla
min
e
panto
then
ate
AD
P-3'-
phosp
hate
Coen
zym
e A
phosp
hopa
nte
thei
ne
H3N
+C
COO
CH2
SHH
cyst
eine
-
The
pho
spho
pan
teth
ein
e pr
ost
hetic
gr
ou
p o
f AC
P is
deri
ved
fr
om
C
oA
In E.
co
li, A
CP is
a se
para
te 12
5-am
ino
ac
id pr
ote
in, in
m
amm
als
it is
part
o
f FA
S
-
Pho
spho
pan
teth
ein
e(P
an
t) is
cova
len
tly
linke
d vi
a a
ph
osp
hate
est
er
to a
se
rine
O
H o
f th
e ac
yl ca
rrie
r pr
ote
indo
ma
in o
f Fa
tty Ac
id Sy
nth
ase
.
The
lon
g fle
xib
le ar
mo
f pho
spho
pan
teth
ein
e
allo
ws
its th
iol t
o m
ove
from
o
ne
a
ctiv
e si
te to
an
oth
er
with
in th
e
com
ple
x.
OP
OH 2
C
O
OCCCNHCH
2
CH2
CNH
CH3
H3C
HH
O
O
CH2
CH2
SH
O
CH2
CHNH CO
-mer
capt
oet
hyla
min
e
pan
toth
enat
e
se
rine
resid
ue
phosp
hopa
nte
thei
ne
of a
cyl c
arrie
r pr
ote
in
pho
spha
te
-
Indi
vidu
al s
teps
of t
he Fa
tty A
cid
Syn
thas
ere
act
ion
path
way
are
ca
talyz
ed by
the ca
talyt
ic d
om
ain
s lis
ted.
Fatty
Aci
d Sy
ntha
se co
mpl
ex
is a
n obl
igate
di
mer
.
With
in each
m
onom
er,
th
e ord
er
of e
nzy
me do
main
s alo
ng
the pr
imar
y se
quen
ceof t
he pr
ote
in is
sum
mariz
ed
belo
w.
There
is
stil
l deba
te ove
r th
e arr
ange
ment o
f dom
ain
s in
3D w
ithin
th
e co
mpl
ex.
An
ato
mic
reso
lutio
n st
ruct
ure
of
the entir
e co
mpl
ex
has
not y
et be
en ach
ieve
d.
Conde
nsin
g M
alo
nyl
/ace
tyl-C
oA
D
ehyd
rata
se En
oyl
-K
eto
acyl
A
CP Th
ioes
tera
se
Enzym
e (C
ys)
Tran
sacy
lase
(S
er)
Re
duct
ase
Re
duct
ase
(P
ant)
N-
-C
Ord
er of d
om
ain
s in
pr
imar
y st
ruct
ure
o
f mam
mal
ian
Fa
tty A
cid
Syn
thas
e
-
As e
ach
o
f the
su
bstra
tes
ace
tyl-C
oA
& m
alo
nyl-
CoA
bin
d to
th
e co
mpl
ex,
th
e in
itia
l atta
ckin
g gr
ou
p is
th
e o
xyge
n o
f a se
rine
hydr
ox
ylgr
ou
p o
f the
Ma
lon
yl/a
cety
l-Co
A Tr
an
sacy
lase
e
nzy
me
do
ma
in.
Each
a
cety
l or
ma
lon
yl m
oie
tyis
tra
nsi
en
tly in
est
er
linka
ge to
th
is se
rine
hy
dro
xyl,
befo
re be
ing
tran
sfe
rre
d in
to th
ioe
ste
r lin
kage
w
ith th
e
pho
spho
pan
teth
ein
e th
iolo
f the
a
cyl c
arr
ier
pro
tein
(A
CP) d
om
ain
.
Ace
tate
is
su
bse
que
ntly
tra
nsf
err
ed
to a
cy
stei
ne
thio
lof t
he Co
nde
nsi
ng
Enzy
me
do
ma
in.
Conde
nsin
g M
alo
nyl
/ace
tyl-C
oA
D
ehyd
rata
se En
oyl
-K
eto
acyl
A
CP Th
ioes
tera
se
Enzym
e (C
ys)
Tran
sacy
lase
(S
er)
Re
duct
ase
Re
duct
ase
(P
ant)
N-
-C
Ord
er of d
om
ain
s in
pr
imar
y st
ruct
ure
o
f mam
mal
ian
Fa
tty A
cid
Syn
thas
e
-
The
co
nde
nsa
tion
rea
ctio
n (st
ep
3) in
volv
es
deca
rbo
xyla
tion
o
f the
m
alo
nyl
mo
iety
, fo
llow
ed
by a
ttack
o
f the
re
sulta
nt c
arb
an
ion
o
n th
e
carb
on
yl ca
rbo
n o
f the
a
cety
l (or
acy
l) mo
iety
.
Pan
t
SH
Cys
SH
Pan
t
SH
Cys
S C CH3
O
Pan
t
S
Cys
S C CH3
OC CH
2
COO
O
Pan
t
S
Cys
SH
C CH2
C
O
CH3
O
ace
tyl-S
-Co
A H
S-Co
Am
alo
nyl-
S-Co
A H
S-Co
ACO
2
1 2
3
1 M
alonyl
/ace
tyl-C
oA
-A
CP Tr
ansa
cyla
se
2 M
alonyl
/ace
tyl-C
oA
-A
CP Tr
ansa
cyla
se
3 Co
nde
nsin
g En
zym
e (-
Ket
oac
yl Sy
nth
ase)
-
Mec
han
ism o
f ca
rbo
n-ca
rbon
bo
nd
form
atio
n in
fa
tty
aci
d bi
osy
nth
esis
No
tes:
The
CO2
that
w
as ad
ded
in th
e A
CC re
actio
n
is lo
st as
CO
2an
d do
es n
ot a
ppea
r in
th
e fa
tty ac
id.
Loss
o
f CO
2re
sults
in
re
son
ance
-st
abili
zed
carb
anio
n
-
4.Th
e -k
eto
ne
is
re
duce
d to
a
n a
lco
hol b
y e
tran
sfe
r fro
m N
ADPH
.
5.D
ehy
dra
tion
yie
lds
a tra
ns
dou
ble
bo
nd.
6.R
edu
ctio
n by
N
ADPH
yie
lds
a sa
tura
ted
cha
in.
Pan
t
S
Cys
SH
C CH2
C
O
CH3
O
Pan
t
S
Cys
SH
C CH2
HC
O
CH3
Pan
t
S
Cys
SH
Pan
t
S
Cys
SH
NAD
PH NA
DP+
NAD
PH N
ADP+
C CH HC
O
CH3
C CH2
CH2
O
CH3
OH
H 2O
4 5
6
4 -K
etoac
yl-A
CP R
educt
ase
5 -H
ydro
xya
cyl-A
CP D
ehyd
rata
se
6 En
oyl
-A
CP R
edu
ctas
e
-
Follo
win
g tr
ansf
ero
f the
gr
ow
ing
fatty
a
cid
from
pho
spho
pan
teth
ein
e to
th
e Co
nde
nsi
ng
Enzy
me
's
cyst
ein
e su
lfhyd
ryl,
the
cy
cle
be
gin
s a
gain
, w
ith
an
oth
er
ma
lon
yl-Co
A.
Pan
t
S
Cys
SH
C CH2
CH2
O
CH3
Pan
t
SH
Cys
S C CH2
O
CH2
CH3
Pan
t
S
Cys
S C CH2
O
CH2
CH3
C CH2
COO
O
Ma
lon
yl-S-
CoA
HS
-Co
A
7 2
7 Co
nde
nsin
g En
zym
e
2 M
alon
yl/a
cety
l-Co
A-A
CP Tr
ansa
cyla
se (re
peat
).
-
Pro
duct
re
leas
e:
Whe
n th
e fa
tty a
cid
is 16
ca
rbo
n a
tom
s lo
ng,
a
Thio
este
rase
dom
ain
ca
talyz
es
hydr
olys
is o
f the
thio
est
er
linki
ng
the
fa
tty a
cid
to
pho
spho
pan
teth
ein
e.
The
16
-C
satu
rate
d fa
tty a
cid
palm
itate
is th
e fin
al
pro
duct
o
f the
Fa
tty Ac
id Sy
nth
ase
co
mpl
ex.
Conde
nsin
g M
alo
nyl
/ace
tyl-C
oA
D
ehyd
rata
se En
oyl
-K
eto
acyl
A
CP Th
ioes
tera
se
Enzym
e (C
ys)
Tran
sacy
lase
(S
er)
Re
duct
ase
Re
duct
ase
(P
ant)
N-
-C
Ord
er of d
om
ain
s in
pr
imar
y st
ruct
ure
o
f mam
mal
ian
Fa
tty A
cid
Syn
thas
e
-
There
is
som
e evi
dence
th
at t
he 2
copi
es
of t
he m
ulti
-do
main
enzy
me are
alig
ned
antip
aral
lel,
as
belo
w.
In th
e tra
nsf
er
step
the gr
ow
ing
fatty
aci
d is
pre
fere
ntia
lly
pass
ed
from
th
e AC
P ph
osp
hopa
nte
thein
e th
iol o
f one su
bunit
to th
e Co
nde
nsi
ng
Enzy
me cy
stein
e th
iol o
f the
oth
er
subu
nit
of t
he di
mer.
How
ever
in
tra-
subu
nit
subs
trat
e tr
ansf
ers
also
occ
ur.
Pant-
SH H
S-Cy
s
Cy
s-SH
H
S-Pa
nt
Fatty
A
cid
Synth
ase
dim
er
-
Palm
itate
, a
16
-C
satu
rate
d fa
tty a
cid,
is th
e fin
al
pro
duct
o
f the
Fa
tty Ac
id Sy
nth
ase
re
act
ion
s.
Sum
mar
y(ig
no
ring
H+
& w
ate
r):ac
etyl
-Co
A +
7
mal
on
yl-Co
A +
14
NA
DPH
palm
itate
+
7
CO2
+ 14
NA
DP+
+ 8C
oA
Acco
un
ting
for
ATP-
depe
nde
nt s
ynth
esi
s o
f m
alo
na
te:
8ace
tyl-C
oA
+
14
NA
DPH
+
7
ATP
palm
itate
+
14
NA
DP+
+ 8
CoA
+7
AD
P+
7P i
Fatty
a
cid
syn
the
sis
occ
urs
in
th
e cy
toso
l. Ac
ety
l-Co
A ge
ne
rate
d in
m
itoch
on
dria
is
tra
nsp
orte
d to
th
e
cyto
sol v
ia a
sh
uttl
e m
ech
an
ism
in
volv
ing
citr
ate.
-
A m
ole
cule
o
f pa
lmita
te co
sts
~13
6 ATP
8 ac
etyl
~Co
A +
14
N
AD
PH +
6
H+
+ 7
ATP
pa
lmita
te +
14
N
AD
P++
8
CoA
+ 6
H2O
+
7
AD
P
8 ac
etyl
~Co
A@
10
AT
P/ac
etyl
~Co
A 80
AT
P14
N
AD
PH@
3.
5 ATP
/NA
DPH
49 AT
P7
ATP
7
ATP
Tota
l 13
6 ATP
-
-Oxi
datio
n &
Fatty
Ac
id Sy
nth
esi
sCo
mpa
red
Ox
ida
tion
Pa
thw
ay
Fatt
y A
cid
Syn
thes
is
path
wa
y lo
catio
n
mito
cho
ndr
ial m
atrix
cy
toso
l
acy
l ca
rrie
rs
(thio
ls )
Coen
zym
e-A
pho
spho
pan
teth
ein
e (A
CP) &
cy
stei
ne
e a
ccep
tors
/do
no
r
FAD
&
N
AD
+
NA
DPH
-O
H
inte
rmed
iate
L D
2-C
pr
odu
ct/d
on
or
acet
yl-Co
A
mal
on
yl-Co
A
(& ac
etyl
-Co
A)
-
Fatty
Ac
id Sy
nth
ase
is
tr
ansc
riptio
nal
ly re
gula
ted.
In liv
er:
In
sulin
, a
ho
rmo
ne
pr
odu
ced
whe
n bl
oo
d gl
uco
se is
hi
gh, st
imu
late
sFa
tty Ac
id Sy
nth
ase
exp
ress
ion
.
Thu
s e
xce
ss gl
uco
se is
st
ore
d a
s fa
t.Tr
an
scrip
tion
fa
cto
rs th
at t
hat m
edi
ate
th
e
stim
ula
tory
e
ffect
o
f in
sulin
in
clu
de US
Fs(up
stre
am
st
imu
lato
ry fa
cto
rs) a
nd
SREB
P-1.
SREB
Ps(st
ero
l re
spo
nse
e
lem
en
t bin
din
g pr
ote
ins)
w
ere
fir
st id
en
tifie
d fo
r th
eir
regu
latio
n
of c
hole
ste
rol s
ynth
esi
s.
Polyu
nsa
tura
ted
fatty
ac
ids
dim
inis
htra
nsc
riptio
n o
f the
Fa
tty Ac
id Sy
nth
ase
ge
ne
in
live
r ce
lls, by
su
ppre
ssin
g pr
odu
ctio
n o
f SR
EBPs
.
-
Elo
nga
tion
beyo
nd
the
16
-C
len
gth
of t
he
palm
itate
pr
odu
ct o
f Fa
tty Ac
id Sy
nth
ase
o
ccu
rs in
mito
cho
ndr
ia a
nd
en
dopl
asm
ic re
ticu
lum
(E
R).
Fa
tty a
cid
elo
nga
tion
w
ithin
m
itoch
on
dria
invo
lve
s th
e -o
xida
tion
pa
thw
ay
run
nin
g in
reve
rse
, e
xce
pt th
at N
ADPH
se
rve
s a
s e
lect
ron
don
or
for
the
fin
al r
edu
ctio
n st
ep.
Po
lyun
satu
rate
d fa
tty a
cids
e
ste
rifie
d to
coe
nzy
me
A
are
su
bstra
tes
for
the
ER
elo
nga
tion
m
achi
ner
y, w
hich
u
ses
ma
lon
yl-Co
A a
s do
no
r o
f 2-ca
rbo
n u
nits
.
-
Des
atu
rase
sin
trodu
ce do
ubl
e bo
nds
at s
peci
fic
posi
tion
s in
a
fa
tty a
cid
cha
in.
Ma
mm
alia
n ce
lls a
re u
na
ble
to
pr
odu
ce do
ubl
e
bon
ds a
t ce
rtain
lo
catio
ns,
e
.g.
, 1
2 .
Thu
s so
me
po
lyun
satu
rate
d fa
tty a
cids
a
re
diet
ary
esse
ntia
ls, e
.g.
, lin
ole
ic a
cid,
18
:2 ci
s 9
,12
(18 C
ato
ms
lon
g, w
ith ci
s do
ubl
e bo
nds
a
t ca
rbo
ns
9-10
&
12-13
).
CO
OH
910
ole
ate
18
:1 ci
s 9
-
Form
atio
n of a
do
ubl
e bo
nd
in a fa
tty a
cid
invo
lves
the
follo
win
g endo
plasm
ic r
etic
ulu
m m
em
brane pr
ote
ins
in
mam
malia
n ce
lls:
N
AD
H-cy
t b5 R
edu
ctas
e, a fla
vopr
ote
in w
ith FA
Das
prost
hetic
gro
up.
Cy
toch
rom
e b 5
, w
hich
m
ay
be a se
para
te pr
ote
in or
a
dom
ain
at o
ne end
of t
he de
satu
rase
.
D
esat
ura
se, w
ith an act
ive si
te th
at c
onta
ins
two
iro
n
ato
ms
com
plexe
d by
his
tidin
e re
sidu
es.
CO
OH
910
ole
ate
18
:1 ci
s 9
-
The
de
satu
rase
ca
talyz
es
a m
ixed
fu
nct
ion
o
xid
atio
nre
act
ion
.
The
re is
a
4-
elec
tro
nre
duct
ion
o
f O2
2 H
2Oa
s a
fatty
a
cid
is o
xidi
zed
to fo
rm a
do
ubl
e bo
nd.
2e
pass
fro
m N
AD
Hto
th
e de
satu
rase
vi
a th
e
FAD
-co
nta
inin
g re
duct
ase
&
cyto
chro
me
b 5
, th
e
ord
er
of e
lect
ron
tra
nsf
er
bein
g:
NA
DH
FA
D
cyt b
5
desa
tura
se
2e
are
e
xtra
cte
d fro
m th
e fa
tty a
cid
as
the
do
ubl
e
bon
d is
fo
rme
d.E.
g., th
e o
vera
ll re
act
ion
fo
r de
satu
ratio
n o
f ste
ara
te
(18:0
) to fo
rm o
lea
te (18
:1 ci
s 9
) is:
stea
rate
+
N
AD
H +
H
++
O
2
ole
ate
+ N
AD
++
2H
2O
-
tric
arb
ox
yla
te tr
an
spo
rt sy
stem
fo
r tr
an
sfer
o
fa
cety
l Co
A fr
om
m
itoch
on
drio
n to
cy
toso
l
Citr
ate
ca
rrie
s a
cety
l gro
ups
fr
om
th
e m
itoch
on
drio
n to
th
e cy
toso
l fo
r
fatt
y a
cid
syn
thes
is
Ace
tyl~
CoA
is ge
ner
ated
in
th
e m
itoch
on
drio
n
by py
ruv
ate
dehy
dro
gen
ase.
Ex
cess
ac
etyl
~Co
Ais
ship
ped
to th
e cy
toso
l fo
r st
ora
ge as
fa
t.
Citr
ate
is pa
ssed
to
th
e ct
yto
sol.
ATP-
citr
ate
lyas
e re
gen
erat
es th
e ac
etyl
~Co
A an
d O
AA
in cy
toso
l.
Mal
ic en
zym
e pr
odu
ces
the
NA
DPH
th
at m
ay be
use
d in
fa
tty ac
id sy
nth
esis.
-
Reg
ula
tion
o
f Fa
tty
Aci
d M
eta
bolis
m
Fatty
ac
id m
etab
olis
m is
coo
rdin
ated
with
o
ther
as
pect
s o
f met
abo
lism
.
Ho
rmo
nal
ly re
gula
ted
by pa
ncr
eatic
a an
d b
cells
, w
hich
se
nse
m
etab
olic
stat
us
and
secr
ete
glu
cago
n an
d in
sulin
,
resp
ectiv
ely.
The
simu
ltan
eou
s sy
nth
esis
and
ox
idat
ion
of f
atty
ac
ids
in liv
er ce
lls is
prev
ente
d.M
alo
nyl
~Co
A in
hibi
ts ca
rniti
ne
palm
itoyl
tran
sfer
ase
I.
Lon
g te
rm re
gula
tion
-sy
nth
esis
of A
CCad
ipo
se lip
popr
ote
in lip
ase,
an
d FA
Sst
imu
late
d by
in
sulin
, in
hibi
ted
by
glu
cago
n, ep
inep
hrin
e.
A di
et hi
gh in
po
lyu
nsa
tura
ted
FA al
so
cau
ses
decr
ease
d FA
S, A
CC.