LIPID METABOLISM &

BETA OXIDATION OF FATTY ACIDS

 LIPID METABOLISM
 Lipids - compounds which are insoluble in water but soluble
in organic solvents. Ex - oils, waxes, and steroids.
 Triacylglycerol - stored fat in adipose tissue - 85 to 90% of
body lipids.
 1gm of lipid - 9Kcal.
 Lipolyisis - the breakdown of fats and other lipids by
hydrolysis to release fatty acids.
 (Lipolyisis = Glycerol + Free fatty acids).
 Lipogenesis - the conversion of fatty acids and glycerol into
fats / formation of fats from surplus glucose.
 Importance of β – Oxidation
 The fatty acids released in the adipocytes enter the circulation and
are transported in a bound form to albumin.
 About 95% of the energy obtained from fat comes from the
oxidation of fatty acids.
 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.
 process of lipolysis of TG and resterification of FFA to TG is
termed as triacylglycerol/fatty acid cycle.
 BETA OXIDATION

 β-Oxidation may be defined as the oxidation(mitochondrial

aerobic process) of fatty acids on the β -carbon atom breaking
down fatty acid into 2C compound acetyl-CoA.
 Other types of oxidations:
• α – oxidation (ER).
• ω - oxidation (ER/mit).
• Oxidation of odd chain F A (mit).
• Oxidation of USFA (mit).
• Oxidation of VLCFA (mit/peroxisomes).
 FATTY ACID OXIDATION - STAGES AND TISSUES

 The β - oxidation of fatty acids involves three stages

I. Activation of fatty acids - cytosol

II .Transport of fatty acids into mitochondria

III. β -Oxidation proper - mitochondrial matrix.

a. Oxidation

b. Hydration

c. Oxidation

d. Cleavage
 I. FATTY ACID ACTIVATION
 Fatty acids are activated to acyl CoA by thiokinases or acyl CoA
synthetases. (its two steps and requires ATP, coenzyme A and
Mg2+).
 Fatty acid + ATP -- acyladenylate
 acyladenylate + coenzyme A = acyl CoA
 two high energy phosphates are utilized, since ATP is converted
to PPi. The enzyme inorganic pyrophosphatase hydrolyses PPi to
phosphate (Pi).
 The immediate elimination of PPi makes this reaction totally
irreversible.
II. TRANSPORT OF ACYL COA INTO MITOCHONDRIA

 The inner mitochondrial membrane is impermeable to fatty acids.

 A specialized carnitine carrier system (carnitine shuttle)
operates.

1. Acyl group of acyl CoA is transferred to Carnitine catalysed by

carnitine acyltransferase I (CAT 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 (Translocase).
3. Carnitine acyl transferase II (CAT II) (inner surface of inner
mit mem) converts acyl-carnitine to acyl CoA.

4. The carnitine released returns to cytosol for reuse.

 III. Β-OXIDATION PROPER
 Each cycle of β -oxidation, liberating a two carbon unit-acetyl
CoA, occurs in a sequence of four reactions.

a. Oxidation : Acyl CoA ---- dehydrogenation(acyl CoA dehydrogenase)

-- A
double bond is formed between α and β carbons (i.e., 2 and 3
carbons).

b. Hydration : Enoyl CoA hydratase brings about the hydration of

the double bond to form β -hydroxyacyl CoA.
c. Oxidation : β -Hydroxyacyl CoA dehydrogenase catalyses the
second oxidation and generates NADH. The product formed is β -
ketoacyl CoA.

d. Cleavage : The final reaction in β -oxidation is the liberation of

a 2 carbon fragment, acetyl CoA from acyl CoA. This occurs by
a thiolytic cleavage catalysed by β –ketoacyl CoA thiolase (or
simply thiolase).
 The new acyl CoA, containing two carbons less than the
original, reenters the beta-oxidation cycle. The process
continues till the fatty acid is completely oxidized.
 Palmitoyl CoA (16C) undergoes 7 cycles of β -oxidation to
yield 8 acetyl CoA, 7FADH2, 7 NADH. Acetyl CoA can enter

citric acid cycle and get completely oxidized to CO 2 and H2O.

ENERGETICS

 E.g., Palmitic acid

 The standard free energy of palmitate = 2,340 Cal.
 The energy yield by its oxidation: 106 ATP (106 × 7.3
Cal) = 940 KCal.
 The efficiency of energy conservation by fatty acid
oxidation = 940 / 2, 340 × 100 = 40%.
 FATTY ACID OXIDATION - STAGES AND TISSUES

 The β - oxidation of fatty acids involves three stages

I. Activation of fatty acids - cytosol

II .Transport of fatty acids into mitochondria

III. β -Oxidation proper - mitochondrial matrix.

a. Oxidation

b. Hydration

c. Oxidation

d. Cleavage
REGULATION

 Mainly through carnitine shutle

 Well fed state  insulin is high as compared to glucagon
-- FA syn -- Malonyl CoA formation- which
inhibits Carnitine shuttle
 Starvation -- Malonyl CoA synthesis is inhibited so
beta oxidation is stimulated.
DISORDERS OF BETA – OXIDATION OF FATTY ACIDS
 Sudden infant death syndrome (SIDS): a disorder due to
blockade in β-oxidation
 It is unexpected death of healthy infants, usually overnight.
 It is now estimated that at least 10% of SIDS is due to
deficiency of medium chain acyl CoA dehydrogenase (1 in
10,000 births).
 After glucose store depletion due to blockade in β –oxidation
of medium chain fatty acids caused by a deficiency in medium
chain acyl CoA dehydrogenase (MCAD) causes SIDS.
 Jamaican vomiting sickness:
 This disease is characterized by severe hypoglycemia, vomiting,
convulsions, coma and death.
 It 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.
 OXIDATION OF ODD CARBON CHAIN FATTY ACIDS

 The β-oxidation of saturated fatty acids containing odd number

of carbon atoms proceeds in the same manner, as even carbon
fatty acids. The only difference is that in the last and final β -
oxidation cycle, a three-carbon fragment is left behind.
 This compound is propionyl CoA which is converted to
succinyl CoA
1.Propionyl CoA is carboxylated in the presence of ATP, CO2 and
vitamin biotin to D-methylmalonyl CoA.

2. D - Methylmalonyl CoA is coverted to L-form by Methylmalonyl

CoA racemase .

3. The next enzyme, methylmalonyl CoA mutase, is dependent on

vitamin B12. It catalyses the conversion of methylmalonyl CoA to
succinyl CoA.