The document discusses lipid metabolism and fatty acid oxidation. Key points include: 1) Lipids are broken down into glycerol and fatty acids through lipolysis. Fatty acids then undergo beta-oxidation in the mitochondria to produce acetyl-CoA. 2) Beta-oxidation involves removing two-carbon units from the fatty acid in repeated cycles to generate acetyl-CoA. This provides energy in the form of ATP. 3) Fatty acid oxidation yields more ATP than carbohydrate oxidation per unit of oxygen consumed. Oxidation of palmitic acid generates 106 ATP through beta-oxidation.

1. Dr. Ifat Ara Begum
Assistant Professor
Dept of Biochemistry
Dhaka Medical College, Dhaka

2.  The breakdown of lipids and involves
hydrolysis
of triglycerides into glycerol and three
fatty acids.
 Substrate: TAG (Fat)
 Product: FA & Glycerol
 Compartment: Cytoplasm
 Nature: Catabolic
 Rate limiting enzyme: HSL
 Hormonal control: Stimulated by
glucagon, cortisol, catecholamine.
Inhibited by insulin

3. 3
Hormone: Adrenalin, Catecholamine,
Activates
Adenylyl
Cyclase
Lipolysis
Adipose Cell & Liver
(Cytoplasm)
Cortisol Glucagon
Receptor (7TM)
ATP c-AMP
Activates lipase (HSL)
Triacylglycerols Glycerol +
Fatty acids Blood
Insulin
blocks this
step

4. Reutilization in situ (adipose tissues/
liver) to make TAG.
Diffuses to blood, may bind
to albumin for transport to
surrounding tissues for oxidation /
reesterification to TAG.

5.  Enters the bloodstreams , then goes to
liver for gluconeogenesis / glycolysis /
TAG synthesis
 Can not be used in adipose tissues for
TAG synthesis, as there is no
glycerokinase enzyme in adipose tissues
to activate glycerol to glycerol-3-
phosphate for TAG synthesis.

7.  A fatty acid contains a long
hydrocarbon chain and a terminal
carboxylate group. The hydrocarbon
chain may be saturated (with no
double bond) or may be unsaturated
(containing double bond).
 Fatty acids can be obtained from-
Diet
Adipolysis
De novo synthesis

9. Building blocks of phospholipids and
glycolipids.
Many proteins are modified by
the covalent attachment of fatty acids,
which target them to membrane
locations
Acts as fuel molecules
 Fatty acid derivatives serve as
hormones and intracellular
messengers e.g. steroids, sex
hormones and prostaglandins.

10. 1) Beta oxidation- Major mechanism,
occurs in the mitochondria matrix. 2-C
units are released as acetyl CoA per
cycle.
2) Alpha oxidation- Predominantly takes
place in brain and liver, one carbon is
lost in the form of CO2 per cycle. It is not
an energetic process.
3) Omega oxidation- Minor mechanism,
but becomes important in conditions of
impaired beta oxidation
4) Peroxisomal oxidation- Mainly for the
trimming of very long chain fatty acids.

11.  It is the process through which fatty
acids in the form of Acyl-CoA (active
form) are broken down in the
mitochondria in order to give energy.
 The fatty acyl chain is shortened by
two carbon atoms as a result of one
cycle of beta oxidation and FADH2,
NADH & Acetyl CoA are generated.
 Because oxidation is on the β carbon
and the chain is broken between the α
(2)- and β (3) carbon atoms, hence the
name, β oxidation .

12. Substrate: Fatty Acid
Product: Acetyl CoA
 Site: Liver, lung, heart, adipose tissues,
skeletal muscles, kidney, testes, etc
Compartment: Mitochondria
Nature: Catabolic
Coenzyme needed: NAD. FAD
Rate limiting enzyme: Carnitine
acyltransferase

13. Major source (80%) of energy for heart
Provides energy for gluconeogenesis
Absent in RBC & neuron

14.  Cellular Uptake of FA from plasma
followed by it’s Activation to Fatty Acyl
CoA in Cytoplasm
 Transport/ Translocation Of Activated
Fatty Acyl CoA From Cytoplasm In To
Mitochondrial Matrix
 Degradation Of Fatty Acyl CoA by a
recurring sequence of four reactions:
1) Oxidation by flavin adenine
dinucleotide (FAD)
2) Hydration,
3) Oxidation by NAD+, and
4) Thiolysis (cleavage) by Co ASH

15.  Fatty acids must first be converted to
an active intermediate before they can
be catabolized. This is the only step in
the complete degradation of a fatty
acid that requires energy from ATP.
The activation of a fatty acid is
accomplished in two steps:

17. Fatty acids are activated on the outer
mitochondrial membrane, whereas
they are oxidized in the mitochondrial
matrix.
 Activated long-chain fatty acids are
transported across the membrane by
conjugating them to Carnitine, a
zwitterionic alcohol.

19.  A quaternary ammonium
compound biosynthesized from
the amino acids lysine and methionine
 3-Hydroxy-4-(trimethylazaniumyl)
butanoate
 Required for the transport of fatty
acids from the intermembraneous
space in the mitochondria, into the
mitochondrial matrix during the
breakdown of lipids (fats) for the
generation of metabolic energy

20. Carnitine is obtained from foods,
particularly animal-based foods, and
via endogenous synthesis
 Biosynthesis of carnitine occurs
primarily in the liver and kidneys from
the amino
acids lysine (via trimethyllysine)
and methionine.

21. 1) The acyl group binds to the hydroxyl
group of carnitine to form acyl carnitine.
This reaction is catalyzed by carnitine acyl
transferase I
2) Acyl carnitine is then shuttled across the
inner mitochondrial membrane by
a translocase.
3) The acyl group is transferred back to
CoA on the matrix side of the membrane.
This reaction, which is catalyzed by
carnitine acyl transferase II.
Finally, the translocase returns carnitine to
the cytosolic side in exchange for an
incoming acyl carnitine

24. Energy yield by the complete oxidation
of one mol of Palmitic acid:
The degradation of palmitoyl CoA (C16-
acyl Co A) requires seven reaction
cycles. In the seventh cycle, the C4-
ketoacyl CoA is thiolyzed to two
molecules of acetyl CoA.

25.  Palmitoyl CoA + 7 FAD + 7 NAD +
7 CoA + 7 H2O
->
8 Acetyl CoA + 7 FAD2H + 7 NADH +
7 H+
 106 (129 As per old concept) ATP are
produced by the complete oxidation of
one mol of Palmitic acid.

26.  3 ATPs per NADH = 3 X 7= 21
 2 ATPs per FADH2 = 2 X 7= 14
 12 ATPs per acetyl-CoA = 8 X 12= 96
 Total = (21+ 14+ 96)= 131 ATPs
 2 ATP equivalents (ATP -> AMP + PPi
PPi -> 2 Pi) consumed during
activation of palmitate to Palmitoyl CoA
 Net Energy output- 131-2 = 129 ATP

27.  2.5 ATPs per NADH = 17.5
 1.5 ATPs per FADH2 = 10.5
 10 ATPs per acetyl-CoA = 80
 Total = (17.5+ 10.5+ 80) =108 ATPs
 2 ATP equivalents (ATP -> AMP + PPi
PPi -> 2 Pi) consumed during
activation of palmitate to Palmitoyl CoA
 Net Energy output- 108-2 = 106 ATP

28. Fatty acids with an odd number of
carbon atoms are oxidized by the
pathway of β-oxidation, producing
acetyl-CoA, until a three-carbon
(propionyl-CoA) residue remains. This
compound is converted to Succinyl-
CoA, a constituent of the citric acid
cycle .
Succinyl CoA can be used for
gluconeogenesis, too.

29. The propionyl residue from an odd-chain
fatty acid is the only part of a
fatty acid that is glucogenic. Acetyl
CoA cannot be converted into pyruvate
or Oxaloacetate in animals.

30. A 17-C FA to be oxidized, 7 turn of
beta oxidation will occur successively
to produce 7 acetyl CoA and at the end
of 7th turn, a 3-C propionyl CoA will
be generated.

33. Fat is broken down to FA & glycerol
that are oxidized via beta oxidation &
glycolysis respectively to produce
acetyl CoA.
Acetyl CoA needs TCA cycle to be
oxidized.
OAA (formed from pyruvate by
carboxylation) supports & maintains
TCA cycle as a catalyst & glucose
(carbohydrate) is the primary source of
OAA.

34. So, through OAA , carbohydrate fuels
TCA cycle to continue as a flame in
which acetyl CoA (end product of fat
oxidation) is finally oxidized (burn
out).