1. The document discusses various pathways of fatty acid oxidation including beta-oxidation, alpha-oxidation, and omega-oxidation. 2. Beta-oxidation occurs in the mitochondria and involves the removal of two carbon units from fatty acyl-CoA in repeated cycles to generate acetyl-CoA. 3. Deficiencies in enzymes involved in fatty acid oxidation can cause diseases like Refsum's disease or Zellweger syndrome characterized by neurological symptoms and accumulation of fatty acids.

2.  It includes:
1. Ketone body metabolism: synthesis and
breakdown of ketone bodies.
2. Phospholipid metabolism: synthesis and
breakdown of phospholipid.
3. Glycolipid metabolism: synthesis and
breakdown of Glycolipid .
4. Cholesterol metabolism: synthesis of
cholesterol and its conversion to bile acids,
vitamin D3 and steroid hormones.

4. 4. Peroxisomal β-oxidation of fatty acids

5. 1. Mitochondrial β-oxidation of fatty acids:
 Site is Mitochondrial matrix.
 Major pathway for the oxidation fatty acids
in humans.

6. 2. α-oxidation of fatty acids:
 Site is Microsomes i.e. ER.
 Biological significance is not known.
 Does not requires any coenzymes.
 Does not yields energy.
 Here the fatty acids is not activated to acetyl
CoA and is shortened every time by only one
carbon atom.

7.  Refsum’s disease:
 Results from inherited deficiency of phytanic acid α-
oxidase enzyme which is the α-hydroxylating
enzyme.
 This enzyme is required for the α-oxidation of
phytanic acid which is an branched chain fatty acid.
 Thus phytanic acid starts accumulating in plasma and
various tissues.
 The disease is characterized by neurological
symptoms such as retinitis pigmentosa, peripheral
neuritis, cerebral ataxia.

8. 3. ω-oxidation of fatty acids:
 Site is ER and mitochondria.
 Minor pathway for oxidation of fatty acids.
 Here the oxidation of fatty acid chain occurs
from either of both ends.
 Thus before starting of the oxidation, methyl
group(CH3) or ω group of fatty acid is firstly
oxidized to –COOH group.

9.  This requires cytochrome P-450 ω oxidation
system, and the enzymes alcohol
dehydrogenase and aldehyde dehydrogenase
to form dicarboxylic acid (fatty acid with –
COOH group at both the ends).
 This dicarboxylic fatty acid then enters the
mitochondria and in normal way undergoes
β-oxidation to produce medium chain
dicarboxylic acid such as succinic acid (C4)
or adipic acid (C6).

10.  Due to the inherited deficiency of
mitochondrial medium chain acylCoA
dehydrogenase (MCAD) enzyme, large
amount of dicarboxylic acids (C6-C10) appears
in the urine thus causing dicarboxylic
aciduria as the medium chain dicarboxylic
fatty acids cannot be oxidized.

11. 4. Peroxisomal β-oxidation of fatty acids:
 Peroxisomes (microbodies)
 Oxidation of long chain fatty acids
 No oxidation of short chain fatty acids
 Leads to the formation of acetyl CoA and H2O2
 H2O2 thus formed decomposes to H2O and O2 by
enzyme catalase in peroxisomes.
 This oxidation process ends at octanoyl CoA, so
acetyl CoA and octanoyl CoA are further oxidized in
mitochondria.

12.  Zellweger’s syndrome (cerebrohepatorenal
syndrome):
 A rare inherited disease.
 Peroxisomes are found absent in some types
of cells in human body.
 As a result, the oxidation of long chain fatty
acids does not takes place and it starts
accumulating in different body organs
particularly brain, liver and kidneys.

14.  In this type of oxidation, a fatty acid molecule
is oxidized (dehydrogenated) at β-carbon
atom with successive removal of two carbon
units(two carbon fragments) at a time as
acetyl CoA from the –COOH end of the fatty
acid chain. Fatty acid chain are then left with
the fatty acid molecule shortened by two
carbon atoms. So this type of oxidation is
known as β-oxidation.

15. 1.
β-oxidation of saturated
fatty acids with even
number of carbon atoms
2.
β-oxidation of saturated
fatty acids with odd
number of carbon atoms
3.
β-oxidation of
unsaturated fatty acids

17. Acyl CoA synthetase or thiokinase / Mg2+
R-CH2-CH2-COOH + CoA.SH R-CH2-CH2-CO-S-CoA
Free Fatty acid ATP AMP +2Pi fatty acyl CoA or
active fatty acid
Acyl CoA synthetase catalyzes the formation of thioester linkage
between –COOH group of fatty acid and the thiol group of
coenzyme A to give fatty acyl CoA or active fatty acid.

18.  A free fatty acid is first activated to fatty acyl
CoA or active fatty acid before it undergoes β-
oxidation which is taking place in
mitochondrial matrix.
 Energy is derived when ATP changes to AMP
and PPi.
 This pyrophosphate(PPi) is further immediately
hydrolyzed by enzyme inorganic
pyrophosphatase to 2 Pi.
 Thus two high-energy phosphate bonds are
broken in this reaction.

22.  Carnitine is carrier for fatty acyl CoA present
in mitochondrial membrane.
 It is β-hydroxy-γ-methylammonium
butyrate.
 Synthesized from L-lysine and L-methionine.
 Widely distributed in all the body tissues but
abundantly found in skeletal muscles (1mg/g
dry weight).

23.  Its inherited deficiency impairs the β-
oxidation of long chain fatty acids which
results in hypoglycemia and muscular
weakness.
 Treatment is dietary carnitine therapy.
 Carnitine deficiency may be either due to the
impaired synthesis of carnitine or renal
leakage.

26. Oxidation of fatty acyl CoA
mitochondrial enzyme
acyl CoA dehydrogenase
Δ2-transenoyl CoA
 By the removal of two hydrogen atoms,
each from carbon-2(αC) and carbon-3
(βC).
 Oxidation or dehydrogenation takes
place and it produces a double bond
between α and β-carbons.

27.  FAD acts as an coenzyme and as it is oxidized
form (FAD) by accepting two hydrogen atoms,
it is reduced to FADH2.
 FADH2 is thus reoxidized through
mitochondrial ETC to yield 2ATP (1.5 ATP)

28.  Three isoenzymes for acyl CoA dehydrogenase
has been identified which are specific for :
1. Short chain fatty acids (4-8 carbon atoms)
2. Medium chain fatty acids (4-14 carbon atoms)
3. Long chain fatty acids ( 12-18 carbon atoms).
 The inherited deficiency of medium chain acyl
CoA dehydrogenase (MCAD) impairs the β-
oxidation of medium chain fatty acid which
results in severe hypoglycemia.

29. 1: SIDS
 MCAD deficiency is the major cause of death
in 10% cases of SIDS(sudden infant death
syndrome).
 The deficiency of MCAD is found in about 1 in
10,000 birth and is manifested itself within
the first two years of life.
 SIDS is an unexpected death of healthy
infants usually overnight.

30. 2: Jamaican vomiting sickness:
 Characterized by hypoglycemia, vomiting and
hypoglycemic coma.
 Caused by eating unripened ackee fruit as it
contains the toxin amino acid called as
hypoglycin A.
 This toxin inhibits short and medium chain
acyl CoA dehydrogenase so the β-oxidation
of fatty acids(short and medium) are
impaired.

33.  NAD+ acts as an coenzyme and it is reduced
to NADH.
 NADH is thus reoxidized through
mitochondrial ETC to yield 3ATP (2.5 ATP).

34. Acetyl CoA (two carbon fragments) & new acyl CoA (two carbons
shorter than the original acyl CoA).

35.  Now the new acyl CoA, shortened by two
carbon atoms, re-enters in β-oxidation cycle
for further oxidation.
 All the four reaction of β-oxidation cycle are
repeated for complete oxidation of fatty acid
to yield acetyl CoA.
 In each cycle of β-oxidation, the acyl CoA
loses two carbon atoms as acetyl CoA and the
fatty acid chain is shortened by two carbon
atoms.

37. Palmitoyl CoA (16C) Acyl CoA synthetase /Mg2+ Palmitic acid (16C)
1st NAD+ + FAD +H2O +CoA.SH
β-oxidation AMP + 2Pi ATP +coenzyme A
Cycle NADH +H+ + FADH2 + Acetyl CoA
Acyl CoA (C14)
NAD+ + FAD +H2O +CoA.SH
NADH +H+ + FADH2 + Acetyl CoA
Acyl CoA (C12)
NAD+ + FAD +H2O +CoA.SH
NADH +H+ + FADH2 + Acetyl CoA
Acyl CoA (C10)
NAD+ + FAD +H2O +CoA.SH
NADH +H+ + FADH2 + Acetyl CoA
Acyl CoA (C8)
NAD+ + FAD +H2O +CoA.SH
NADH +H+ + FADH2 + Acetyl CoA
Acyl CoA (C6)
NAD+ + FAD +H2O +CoA.SH
NADH + H+ + FADH2 + Acetyl CoA
Acyl CoA (C4)
NAD+ + FAD +H2O +CoA.SH
NADH + H+ + FADH2 + Acetyl CoA
Acetyl CoA (C2)

38.  Suppose 16 C palmitic acid undergoes seven β-
oxidation cycles.
 In each β-oxidation cycles, there is a loss of
two carbon atoms as acetyl CoA and it gives
one FADH2 and one NADH.
 At the end of complete β-oxidation of palmitic
acid, total of 8 acetyl CoA, 7 FADH2 and 7
NADH is formed.
Palmitoyl CoA +7NAD+ +7FAD +7CoA.SH +7H2O
8 Acetyl CoA +7NADH +7H+ + 7FADH2

40. Step ATP gain
1.Activation of palmitic acid -2 high energy phosphate bond
to palmitoyl CoA.
2. Oxidation of 7FADH2 by ETC (2/1.5 ATP) 7x2=14 ATP (7x1.5=10.5
ATP)
3. Oxidation of 7NADH by ETC (3/2.5 ATP) 7x3=21 ATP (7x2.5=17.5
ATP)
4. Oxidation of 8 acetyl CoA in TCA cycle 12x8=96 ATP (10x8=80 ATP)
(each molecule of acetyl CoA in TCA cycle
gives 12/10 ATP) --------------------
-----------------
131 ATP (108 ATP)
131-2=129ATP 108-
2=106 ATP
129 ATP is gained at the end of complete β-oxidation of palmitic acid according
to old calculation.
106 ATP is gained at the end of complete β-oxidation of palmitic acid
according to new calculation.

41.  Glucose is the principle source of energy under
normal conditions.
 But when hepatic glycogen is exhausted either in
prolonged starvation or in DM when body cells
fails to utilize the available blood glucose(due to
impaired carbohydrate metabolism), β-oxidation
of fatty acids becomes the source of metabolic
energy.

42.  But in many conditions β-oxidation of fatty
acids gets impaired which gives rise to
number of diseases which are often
associated with hypoglycemia.
 The conditions may be:
1. The inherited deficiency of carnitine.
2. Inherited deficiency of enzymes of β-
oxidation pathway such as MCAD, CAT-I,
CATII, acylcarnitine-carnitine translocase.

43.  This may impairs β-oxidation of long chain fatty
acids which results in hypoglycemia and mild to
severe muscular weakness.
 The deficiency may be dietary or may be due to
renal leakage.
 Treatment is dietary carnitine therapy.

44.  As the enzymes named CAT-I and CAT-II
participate in the transport of fatty acyl CoA in to
mitochondrial matrix, but the inherited deficiency
of CAT impairs the β-oxidation of fatty acids and
thus results in hypoglycemia.
 Deficiency of CAT-I primarily affects liver and
deficiency of CAT-II primarily affects skeletal
muscles.

45.  This may lead to intermittent hypoglycemic
coma, muscular weakness and
cardiomyopathy.