section 18.1
Oxidation of Fatty Acids
369
<0
t
.11
<Q
If
O ^
<
©
CÖ
~a
x
o
cû.
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R — C H — C H — C— O H
(A fatty a cid )
C o A S H -
AM P + P P
Mg
A T P —
A cyl-C oA
s y n th e ta se
M any th io k in a ses a re know n.
T h ey differ in their su b stra te
specificity a n d o ccu r in th e outer
m em b ran e o f th e m itochondria
an d m icro so m es.
R — C H ,— CH — O S C o A
T ranslocation to m itochondrial
matrix involving carnitine
M itochondrial I
(A cyl-C oA )
m atrix
R — C H — C H — C ~ S — C oA
F P
-—
—►
R ed . carriers —
— 1
/2 0
2
,2 A D P , 2P,
Y
(respiratory ch ain )
Y
i
------ O x. carriers *—
A cyl-C oA
d e h y d r o g e n a se
►31-1*0,2A T P
FPHj-
trans
I*
CH =
C H — C ~ S — C oA ( a , ß -U n satu rated acyl-C oA or A 2-u nsaturated acyl-C oA )
H ,0
E n oyi-C oA
h y d ra ta se
OH
R— CH — C H — C ~ S — C oA
( l (+)-ß -hydroxy acyl-C oA )
L-l
ß -H ydroxyacyl-C oA
d e h y d r o g e n a se
-N A D -
)
------- — ►
R ed . ca rriers—
w
—
t/ü u
2
.
Y
(respiratory ch ain )
Y
+ H+— ^
------O x. carriers —
4H * 0 ,
►NADH
O
1/2 0 2, 3A D P , 3F>
3A T P
(ß -K etoacyl-C oA )
R — C — C H r - C - S — C oA
C oA S H
9
TC A
c y c le ;
^ C H - C ~ S - C o A ^ respiratory ch ain > 2C Q ^ + 12A T p
(acetyl-C oA ) ■
K eton e b o d ie s (in liver)
3 -K e to a c y l-C o A
th io la s e
-
R — C ~ S — C oA
Fatty acyl-C oA ,
tw o c a rb o n s sh orter
T o cy to so l, for
ch o lestero l sy n th e sis
F I G U R E 1 8 -3
Fatty acid activation, transport, and ^-oxidation. The shortened fatty acyl-CoA from one cycle is further oxidized in
successive passes until it is entirely converted to acetyl-CoA. Odd-chain fatty acids produce one molecule of
propionyl-CoA. Ox. = Oxidized; Red. = reduced; respiratory chain = oxidative phosphorylation and electron transport;
~ = high-energy bond; FP = flavoprotein.
and oxidative decarboxylation of the amino acid
hypoglycin (Chapter 15). Ingestion of hypoglycin
causes severe hypoglycemia due to the inhibition of
/(-oxidation and corresponding decrease in ATP
synthesis. Gluconeogenesis, which is important in
maintaining fasting glucose levels, is dependent on
adequate supplies of ATP. The action of hypoglycin
thus serves to emphasize the importance of
/(-oxidation in gluconeogenesis under normal
circumstances.
Among the fatty acid oxidation disorders,
medium-chain acyl-CoA dehydrogenase deficiency
(MCAD)
is the most common and its frequency is
similar to that of phenylketonuria. The disorder can
be identified by mutant alleles and some key
abnormal metabolites. An A -»■ G transition mutation
occurs at position 985 of MCAD-cDNA in about 90%
of cases. This mutation leads to replacement of lysine
with glutamate at position 329 (K329E) of the
polypeptide.
