β Oxidation of saturated and unsaturated fatty acids

β Oxidation
of
saturated and
unsaturated fatty acids

Objective

       At the end of this lecture, student will be able to

      Explain catabolism of saturated
fatty acids

      Explain catabolism of unsaturated
fatty acids

      Discuss
the diseases associated with enzymatic defects in metabolism of fatty acids

β Oxidation of saturated
fatty acids

       The fatty acids in the body are
mostly oxidized by
β-oxidation

       β-Oxidation may be defined as the oxidation of fatty acids on the β-carbon atom.

       This results in the sequential
removal of a two carbon fragment-acetyl CoA

       β-oxidation of fatty acids involves three stages

                l. Activation of fatty acids
occurring in the cytosol

                ll. Transport of fatty acids
into mitochondria

                lll. β-Oxidation in the mitochondrial matrix

l.
Activation of fatty acids occurring in the cytosol

  • Fatty acids are activated to
    acyl CoA by thiokinases or acyl CoA synthetases

           The reaction occurs in two steps and
requires ATP, coenzyme A & Mg2+

           Fatty acid reacts with ATP to form acyladenylate
which then combines
with coenzyme A to produce acyl CoA

           This reaction totally irreversible

II.
Transport of fatty acids into mitochondria

       This occurs in four steps

1. Acyl CoA
is transferred to carnitine catalysed by carnitine acyltransferase-I (present
on the outer surface of inner mitochondrial membrane)

2. The
acyl-carnitine is transported across the membrane to mitochondrial matrix by a
specific carrier protein

3.
Carnitine acyl transferase-ll (found on the inner surface of inner
mitochondrial membrane) converts acyl-carnitine to acyl CoA

4. The
carnitine released returns to cytosol for reuse. C
arnitine acyl
transferase is inhibited by malonyl CoA

lll. β-Oxidation in the mitochondrial matrix

       Each cycle of β-oxidation, liberating a two carbon unit- acetyl CoA, occurs in a
sequence of four reactions

1.
Oxidation
: Acyl CoA
undergoes dehydrogenation by an FAD-dependent flavoenzyme, acyl CoA
dehydrogenase. A double bond is formed between
α & β carbons

2.
Hydration
: Enoyl
CoA hydratase brings about the hydration of the double bond to form
p-hydroxyacyl CoA

3.
Oxidation
: β-hydroxyacyl CoA dehydrogenase catalyses the second oxidation and
generates NADH. The product formed is
β-ketoacylCoA

4.
Cleavage
: The final
reaction in
β-oxidation is the liberation of 2
carbon fragment, acetyl CoA from acyl CoA. This is by thiolytic cleavage
catalysed by thiolase

       The new acyl CoA, containing two
carbons less than the original, re-enters the
β-oxidation cycle

       The process continues till the fatty
acid is completely oxidized

Beta
oxidation of palmitic acid

Energetics of β-oxidation of palmitic acid

Oxidation
of palmitoyl CoA: Palmitoyl CoA + 7CoASH + 7FAD + 7
NAD+ + 7H2O – —> 8
Acetyl CoA + 7FADH2 +
7NADH + 7H+

       It undergoes 7 cycles of β-oxidation to yield 8 acetyl CoA

       Acetyl CoA can enter citric acid
cycle and get completely oxidized to CO2 & H2O

       Fatty acids are oxidized by most of
the tissues in the body.

       However, brain, erythrocytes and
adrenal medulla cannot utilize fatty acids for energy requirement

Disorders of β-oxidation

       SIDS: The sudden infant death
syndrome (SIDS) is an unexpected death of healthy infants, usually overnight.
It is estimated that at least 10% of SIDS is due to deficiency of medium chain
acyl CoA dehydrogenase

       Jamaican vomiting sickness: This
disease is characterized by severe hypoglycemia, vomiting, convulsions, coma
and death. lt is caused by eating unripe ackee fruit, which contains an unusual
toxic amino acid, hypoglycin A. This inhibits the enzyme acyl CoA dehydrogenase
and thus
β-oxidation of fatty acids is
blocked, leading to various complications.

β Oxidation of unsaturated
fatty acids

       Due to the presence of double bonds,
the unsaturated fatty acids are not reduced to the same extent as saturated
fatty acids. Therefore, oxidation of unsaturated fatty acids, in general,
provides less energy than that of saturated fatty acids

       Most of the reactions involved in
the oxidation of unsaturated fatty acids are the same as found in the
β-oxidation of saturated fatty acids. However, the presence of double
bonds poses problem for
β-oxidation to proceed

       This is overcome by two additional
enzymes-an isomerase and an epimerase

       In
the oxidation of unsaturated fatty acids, most of the reactions are the same as
those for saturated fatty acids, however,2 additional enzymes are required

       The
combined action of isomerase and reductase are needed to degrade a wide range
of unsaturated fatty acids

       Energy
yield is less for the oxidation of unsaturated fatty acids as they are less
reduced

       2
ATPs are less formed per double bond as the first step of dehydrogenation to
introduce the double bond is not required

Summary

       The fatty acids in the body are
mostly oxidized by
β-oxidation

       Oxidation of palmitoyl CoA undergoes
7 cycles of
β-oxidation to yield 8 acetyl CoA

       SIDS & Jamaican vomiting
sickness are due to deficiency of acyl CoA dehydrogenase

       Additional two enzymes- isomerase
and reductase required for oxidation on unsaturated fatty acid





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