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chapter 18
Lipids I: Fatty Acids and Eicosanoids
oxidized and decarboxylated to a fatty acid one carbon
shorter than the original. Thus, if an odd-chain-length
compound is used initially, an even-chain-length acid is
produced that can be further oxidized by /3-oxidation.
OH
R— CH2—CH— COOH
Dehydrogenase
-NAD'
o
R— CH2— C— COOH
Oxidative
decarboxylation
► C02
o
R— CH,— C— OH
In Refsum’s disease, an autosomal recessive disorder,
the defect is probably in the a-hydroxylation of phy-
tanic acid. Phytanic acid is a 20-carbon, branched-chain
fatty acid derived from the plant alcohol phytol, which is
present as an ester in chlorophyll. Thus, its origin in the
body is from dietary sources. The oxidation of phytanic
acid is shown in Figure 18-6. The clinical characteristics
of Refsum’s disease include peripheral neuropathy and
ataxia, retinitis pigmentosa, and abnormalities of skin and
bones. Significant improvement has been observed when
patients are kept on low-phytanic acid diets for prolonged
periods (e.g., diets that exclude dairy and ruminant fat).
ui-Oxidation
«-Oxidation is oxidation of the carbon atom most re-
mote from the carboxyl group in a fatty acid. The ba-
sic reaction, catalyzed by a monooxygenase that requires
NADPH, O
2
, and cytochrome P-450, is shown below. It
has been observed in liver microsomes and some bacteria.
. c^-oxidation
H3C-(CH2)n-COOH + 0 2 + NADPH + H + ---------►
HO-CH2-(CH2)„-COOH + NADP+ + H20
Further oxidation of the «-hydroxy acids produces dicar-
boxylic acids, which can be /J-oxidized from either end.
Oxidation of Mono- and Polyunsaturated
Fatty Acids
Oxidation of unsaturated fatty acids requires A3-cA-,A2-
trans-enoyl-CoA isomerase and NADPH-dependent 2,4-
dienoyl-CoA reductase, in addition to the enzymes of /3-
oxidation. The enoyl-CoA isomerase produces the sub-
strate for the hydration step. The reductase catalyzes the
reduction of A2-fran.v-,A4-c«-decadienoyl-CoA to A3-
fnmv-decenoyl-CoA. The latter is isomerized to A2
-trans-
decenoyl isomerase, which is a normal /3-oxidation inter-
mediate. These reactions are illustrated for oxidation of
oleic and linoleic acids in Figures 18-7 and 18-8.
18.2 Metabolism of Ketone Bodies
Ketone bodies consist of acetoacetate, D-/3-hydroxy-
butyrate (D-3-hydroxybutyrate), and acetone. They are
Phytol
CH,
CH ,
I
CH,
(3 -Oxidation
blocked by the
m ethyl group
.COOH
P hytanic acid (3 ,7 ,1 1 ,15-tetram ethylhexadecanoic acid)
a -Oxidation (block in R efsum 's d ise a se )
CHj
Pristanic acid
I Degradation by p-oxidation
1
a s show n by arrow marks
HC
C H — COOH + 3CH
3
CH2COOH + 3CH.COOH
H3C/
FIGURE 18-6
Oxidation of phytol and phytanic acid.
