376
chapter 18
Lipids I: Fatty Acids and Eicosanoids
3 A cety l C o A -^ jß -O x id a tio n s
-S C o A
A
5
-c/'s- A‘
-as-
D ie n o y l-C o A
(in a c tiv e s u b s tr a te in ß -o x id a tio n )
|A
3
-c/s-A
2
-fra n s-
[E n o y l-C o A is o m e r a s e
A
2
-?rans-A
6
-c /s-D ie n o y l-C o A
(n o rm a l s u b s tr a te in ß -o x id a tio n )
A c ety l C o A —jp - O x id a tio n
O
II
C — S C o A
A
4
-c/'s-en o y l-C o A
A cy l-C o A d e h y d r o g e n a s e
O
- S C o A
5
4 ,,a " s '2
A
2
-trans-
A
4
-cis
D ie n o y l-C oA
|2 ,4 -D ie n o y l-C o A r e d u c ta s e
4
't r a n ig
" C — S C o A
A
3
-f/a n s -E n o y l-C o A
0
E n o y l-C o A is o m e r a s e
F I G U R E 1 8 -8
Oxidation of linoleic acid.
A -fra n s-E n o y l-C o A
|ß - O x id a tio n s
5 A cety l-C o A
trans
C — S C o A
O
Physiological and Pathological Aspects
of Metabolism of Ketone Bodies
Acetoacetate and
p
-hydroxybutyrate are products of nor-
mal metabolism of fatty acid oxidation and serve as
metabolic fuels in extrahepatic tissues. Their level in blood
depends on the rates of production and utilization. Oxida-
tion increases as their plasma level increases. Some extra-
hepatic tissues (e.g., muscle) oxidize them in preference to
glucose and fatty acid. Normally, the serum concentration
of ketone bodies is less than 0.3 mM/L.
The rate of formation of ketone bodies depends on the
concentration of fatty acids derived from hydrolysis of
adipose tissue triacylglycerol by hormone-sensitive lipase.
Insulin depresses lipolysis and promotes triacylglycerol
synthesis and storage, while glucagon has the opposite
effects. Thus, insulin is antiketogenic and glucagon is
ketogenic (Chapter 22). Uncontrolled insulin-dependent
diabetes may result in fatal ketoacidosis (Chapter 39). Al-
though ketonemia and ketonuria are generally assumed to
be due to increased production of ketone bodies in the
liver, studies with depancreatized rats have shown that
ketosis may also arise from their diminished oxida-
tion.
Ketosis can occur in starvation, in ethanol abuse, and
following exercise, the last because of a switch in blood
