Page 175 - Color Atlas of Biochemistry

P. 175

166 Metabolism

Minor pathways of fatty acid boxylic acid cycle and is available for gluco-
degradation neogenesis through conversion into oxaloace-
tate. Odd-numbered fatty acids from pro-
Most fatty acids are saturated and even-num- pionyl-CoA can therefore be used to synthe-
bered. They are broken down via E-oxidation size glucose.
(see p.164). In addition, there are special path- This pathway is also important for rumi-
ways involving degradation of unsaturated nant animals, which are dependent on sym-
fatty acids (A), degradation of fatty acids biotic microorganisms to break down their
with an odd number of C atoms (B), α and ω food. The microorganisms produce large
oxidation of fatty acids, and degradation in amounts of propionic acid as a degradation
peroxisomes. product, which the host can channel into the
metabolism in the way described.

A. Degradation of unsaturated fatty acids
Further information
Unsaturated fatty acids usually contain a cis
double bond at position 9 or 12—e. g., linoleic In addition to the degradation pathways de-
acid (18:2; 9,12). As with saturated fatty acids, scribed above, there are also additional spe-
degradationinthis case occurs via β-oxida- cial pathways for particular fatty acids found
tion until the C-9-cis double bond is reached. in food.
Since enoyl-CoA hydratase only accepts sub- a Oxidation is used to break down methyl-
strates with trans double bonds, the corre- branched fatty acids. It takes place through
sponding enoyl-CoA is converted by an iso- step-by-step removal of C 1 residues, begins
6
3
merase from the cis-∆ , cis- ∆ isomer into the with a hydroxylation, does not require coen-
6
3
trans-∆ ,cis-∆ isomer [1]. Degradation by β- zyme A, and does not produce any ATP.
oxidation can now continue until a shortened w Oxidation—i. e., oxidation starting at the
2
4
trans-∆ , cis-∆ derivative occurs in the next end of the fatty acid—also starts with a hy-
cycle. This cannot be isomerized in the same droxylation catalyzed by a monooxygenase
way as before, and instead is reduced in an (see p. 316), and leads via subsequent oxida-
3
NADPH-dependent way to the trans-∆ com- tion to fatty acids with two carboxyl groups,
pound [2]. After rearrangement by enoyl-CoA which can undergo β-oxidation from both
isomerase [1], degradation can finally be com- ends until C 8 or C 6 dicarboxylic acids are
pleted via normal β-oxidation. reached, which can be excreted in the urine
in this form.
Degradation of unusually long fatty acids.
B. Degradation of oddnumbered fatty acids An alternative form of β-oxidation takes place

Fatty acids with an odd number of C atoms are in hepatic peroxisomes,which arespecialized
treated in the same way as “normal” fatty for the degradation of particularly long fatty
acids—i. e., they are taken up by the cell with acids (n > 20). The degradation products are
ATP-dependent activation to acyl CoA and are acetyl-CoA and hydrogen peroxide (H 2 O 2 ),
transported into the mitochondria with the which is detoxified by the catalase (see
help of the carnitine shuttle and broken p. 32) common in peroxisomes.
down there by β−oxidation (see p. 164). In
the last step, propionyl CoA arises instead of Enzyme defects are also known to exist in
acetyl CoA. This is first carboxylated by pro- the minor pathways of fatty acid degradation.
pionyl CoA carboxylase into (S)-methylmalonyl In Refsum disease, the methyl-branched phy-
CoA [3], which—after isomerization into the tanic acid (obtained from vegetable foods)
(R) enantiomer (not shown; see p. 411)—is cannot be degraded by α-oxidation. In Zell-
isomerized into succinyl CoA [4]. weger syndrome, a peroxisomal defect means
Various coenzymes are involved in these that long-chain fatty acids cannot be de-
reactions. The carboxylase [3] requires biotin, graded.
and the mutase [4] is dependent on coenzyme
B 12 (5 -deoxyadenosyl cobalamin; see p. 108).
Succinyl-CoA is an intermediate in the tricar-

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