Synthesis of Long-Chain Saturated Fatty Acids
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,
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 -
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.
malonyl-CoA, by a slightly modified reversal of
oxidation. The substrates are saturated and unsaturated
, and C;f, fatty acids, and the products are Q g,
, and C
fatty acids. The first reduction step
utilizes NADH, and the enzyme is /1-hydroxyacyl dehy-
-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)
L inoleoyl-C oA
(o cta d eca d ien o y l-C o A )
H++ N A D (P)H + Q - J
d e sa tu r a se
N A D (P) + 2H
0 ~ V
7-L inolenoyl-C oA , C 1 8 :3 (6 ,9 ,1 2 )
(o ctad ecatrien oyl-C oA )
(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 )
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.