section 18.4
Synthesis of Long-Chain Saturated Fatty Acids
385
FIGURE 18-13
Cytoplasmic generation of acetyl-CoA via citrate transport and related reactions. PPP = Pentose phosphate pathway;
FAS = fatty acid synthase. —©->■ Negative allosteric modifier. —©-»■ Positive allosteric modifier.
As a result, acetyl-CoA carboxylase and citrate synthase
are inhibited. The stimulatory effect of prolactin is con-
fined to the mammary gland and may involve synthesis
of the enzyme.
Mitochondrial fatty acid elongation occurs primarily when
the [NADH]/[NAD+] ratio is high (e.g., anaerobiosis, ex-
cessive ethanol oxidation).
Fatty Acid Elongation
Cytoplasmic fatty acid synthase yields palmitate. Human
triacylglycerol contains fatty acids with 18,
2 0
,
2 2
, and
24 carbon atoms, which are synthesized by elongation
of palmitate in endoplasmic reticulum or mitochondria.
Elongation in the endoplasmic reticulum occurs mainly in
liver and involves Q o -
1 6
—
saturated and Cis-unsaturated
fatty acids by successive addition of two-carbon groups
derived from malonyl-CoA (Figures 18-14 and 18-15).
The reductant is NADPH. The intermediates, however,
are CoA thioesters.
The
mitochondrial
system
uses
acetyl-CoA,
not
malonyl-CoA, by a slightly modified reversal of
ß-
oxidation. The substrates are saturated and unsaturated
C
1 2
, C]
4
, and C;f, fatty acids, and the products are Q g,
C
2 0
»
C
2 2
, and C
2 4
fatty acids. The first reduction step
utilizes NADH, and the enzyme is /1-hydroxyacyl dehy-
drogenase (a
ß
-oxidation enzyme); the second reduction
step utilizes NADPH, and the enzyme is enoyl reductase.
Linoleic acid , C 1 8 :2 (9 ,1 2 ) (from th e diet)
(o cta d ec a d ien o ic acid)
A ctivation
L inoleoyl-C oA
(o cta d eca d ien o y l-C o A )
H++ N A D (P)H + Q - J
.
, C
6
d e sa tu r a se
N A D (P) + 2H
2
0 ~ V
7-L inolenoyl-C oA , C 1 8 :3 (6 ,9 ,1 2 )
(o ctad ecatrien oyl-C oA )
a-
(M alonyl-C oA ,
2N A D P H )
C h ain -elon gation sy s te m
D ih o m o -Y-linolenoyi-C oA , C 2 0 :3 (8 ,1 1 ,1 4 )
(eicosatrien oyl-C oA )
H++ NAD(P)H + O -
NAD(P)++ 2H20 - ' f
A rachidonoyl-C oA , C 2 0 ;4 (5 ,8 ,1 1 ,1 4 )
(eico sa tetra en o y l-C o A )
C
5
d e sa tu r a se
F IG U R E 1 8 -1 4
Synthesis of arachidonic acid from linoleic acid. The desaturation and
chain elongation occur in microsomes.
