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8/8/2019 Degradation of Fatty Acids
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Degradation of Fatty Acidsy Occurs in Mitochondria.y Free fatty acidsalso called unesterified (UFA) or
nonesterified fatty acids (NEFA) are fatty acidsthat are in the unesterified state.
y In plasma, longer-chain FFA are combined withalbumin, and in the cell they are attached to a
fatty acid-binding protein, so that in fact they are never really free. Shorter-chain fatty acids aremore water-soluble and exist as the un-ionizedacid or as a fatty acid anion.
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y Fatty acids must first be converted to an activeintermediate before they can be catabolized.
y This is the only step in the complete degradationof a fatty acid that requires energy from ATP.
y In the presence of ATP and coenzyme A, theenzyme acyl-CoA synthetase (thiokinase)catalyzes the conversion of a fatty acid (or freefatty acid) to an active fatty acid or acyl-CoA, which uses one high-energy phosphate with the
formation of AMP and PPi.
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Mitochondrial oxidation of fatty acids takes place in threestages (In the first stagebeta oxidationfatty acidsundergo oxidative removal of successive two-carbon unitsin the form of acetyl-CoA, starting from the carboxyl end of the fatty acyl chain.
The overall result is the conversion of the
16-carbon chain of palmitate to eight two-carbon acetyl
groups of acetyl-CoA molecules. Formation of each
acetyl-CoA requires removal of four hydrogen atoms
( two pairs of electrons and four H) from the fatty acyl
moiety by dehydrogenases.
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In the second stage of fatty acid oxidation, the
acetyl groups of acetyl-CoA are oxidized to CO2 in the
citric acid cycle, which also takes place in themitochondrial matrix. Acetyl-CoA derived from fatty acids thus enters a final common pathway of oxidation
with the acetyl-CoA derived from glucose via glycolysis
and pyruvate oxidation.
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The first two stages of fatty acid oxidation produce thereduced electron carriers NADH and FADH2, which in
the third stage donate electrons to the mitochondrialrespiratory chain, through which the electrons pass tooxygen with the concomitant phosphorylation of ADPto ATP .The energy released by fatty acid oxidation is
thus conserved as ATP.
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y
The PPi is hydrolyzed by inorganicpyrophosphatase with the loss of a further high-energy phosphate, ensuring that the overall reactiongoes to completion.
y Acyl-CoA synthetases are found in the endoplasmicreticulum, peroxisomes, and inside and on the outermembrane of mitochondria.
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y -OXIDATION OF FATTY ACIDS INVOLVESSUCCESSIVE CLEAVAGE WITH RELEASE OF
ACETYL-CoA.y In -oxidation , two carbons at a time are cleaved
from acyl-CoA molecules, starting at the carboxylend.
y The chain is broken between the (2)- and (3)-carbon atomshence the name -oxidation.
y The two-carbon units formed are acetyl-CoA; thus,
palmitoyl- CoA forms eight acetyl-CoA molecules.
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Role of carnitine in the transport of
long-chain fatty acids through the inner
mitochondrial membrane. Long-chain
acyl-CoA cannot pass through the inner
mitochondrial membrane, but its
metabolic product, acylcarnitine, can.
