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chapter 18
Lipids I: Fatty Acids and Eicosanoids
T A B L E 1 8 -1
Naturally Occurring Saturated Fatty Acids
Common Name
Systematic Name*
Molecular Formula
Structural Formula
Melting Point (°C)
Capric
n-Decanoic
C 10^20^2
CH3[CH2]8COOH
31
Laurie
n-Dodecanoic
C 12^24^2
CH9[CH9],nCOOH
44
Myristic
n-Tetradecanoic
Ci4H2802
CH,[CH7]19COOH
58
Palmitic'1
'
n-Hexadecanoic
^16^32^2
CH3[CH2]14COOH
63
Stearic'1
'
R-Octadecanoic
^•18^36^2
CH3[CH2]16COOH
70
Arachidic
R-Eicosanoic
^20^40^2
CH9[CH9],sCOOH
76
Behenic
n-Docosanoic
^22^44^2
CH9[CH9]9nCOOH
80
Lignoceric
n-Tetracosanoic
C
2
4H4802
CH9[CH9]99COOH
84
Cerotic
«-Hexacosanoic
^-26^52^2
CH3[CH2]24COOH
88
Montanic
R-Octacosanoic
c 28h 56o 2
CH3[CH2]26COOH
92
♦ Systematic name is based on replacing the final letter “e” of the parent hydrocarbon with “oic.”
^Most abundant fatty acids present in animal lipids.
lipoproteins is discussed in Chapter 20. Fatty acids are
released by hydrolysis of triacylglycerol in adipocytes by
hormone-sensitive lipase, particularly during starvation,
stress, and prolonged exercise (Chapter 22).
Interrelationships of tissues in lipid metabolism are dis-
cussed in Chapter 22.
18.1
Oxidation of Fatty Acids
The overall fatty acid oxidation process in mitochondria
consists of uptake of fatty acids, their activation to acyl-
CoA, then to thioesters, and finally translocation into mi-
tochondria which involves a carnitine transesterification
shuttle and ^-oxidation. Fatty acids released from chy-
lomicrons and VLDLs are transferred across cell mem-
branes by passive diffusion, which depends on the con-
centration gradient. Fatty acids are also obtained from the
hydrolysis of triacylglycerol stored in adipose tissue which
are bound to albumin and transported in blood. Fatty acids
serve as substrates for energy production in liver, skeletal
and cardiac muscle during periods of fasting. Although
the brain does not utilize fatty acids for generating energy
directly, brain cells can utilize ketone bodies synthesized
from acetyl-CoA and acetoacetyl-CoA. The latter two are
obtained from /3-oxidation of fatty acids in the liver. All
of the enzymes involved in mitochondrial fatty acid
/3-
oxidation are encoded by nuclear genes. After their syn-
thesis in the cytosolic endoplasmic reticulum, the enzymes
are transported to mitochondria. The transport of the en-
zymes into mitochondria, in many instances, requires the
presence of N-terminal extensions to guide the protein
across the mitochondrial membrane, receptor-mediated
ATP-dependent uptake, and proteolytic processing to form
fully assembled, mature enzymes. During /3-oxidation of
acyl-CoA, the chain length of the substrate is shortened
by two carbon atoms (acetyl-CoA) each cycle. Thus,
ß-
oxidation requires a group of enzymes with chain length
specificity.
Activation of Fatty Acids
At least three acyl-CoA synthases, each specific for a par-
ticular size of fatty acid, exist: acetyl-CoA synthase acts on
acetate and other low-molecular-weight carboxylic acids,
medium-chain acyl-CoA synthase on fatty acids with
4-11 carbon atoms, and acyl-CoA synthase on fatty acids
with 6-20 carbon atoms. The activity of acetyl-CoA syn-
thase in muscle is restricted to the mitochondrial matrix.
Medium-chain acyl-CoA synthase occurs only in liver mi-
tochondria, where medium-chain fatty acids obtained from
digestion of dietary triacylglycerols and transported by
the portal blood are metabolized. Acyl-CoA synthase, the
major activating enzyme, occurs on the outer mitochon-
drial membrane surface and in endoplasmic reticulum. The
overall reaction of activation is as follows:
R C O C T + A T P 4 “ + C o A S H
O
R C — S C o A + A M P 2 “ + P P 2 “
A cy l-C o A
( a th io e s te r )
The reaction favors the formation of fatty acyl-CoA, since
the pyrophosphate formed is hydrolyzed by pyrophos-
phatase: PP; + H
2
O —►
2P;. Thus, activation of a fatty
