Metabolism of the lipids
Fatty acids have 4 major roles in the cell:
 Building blocks of phospholipids and glycolipids
Added onto proteins to create lipoproteins, which targets them
to membrane locations
Fuel molecules - source of ATP
Fatty acid derivatives serve as hormones and intracellular
messengers

Omega-3 f.acids shown to
slow the development of
cardiovascular diseases

 The oxidation of f.acids – source of energy in the catabolism of lipids
 Both triacylglycerols and phosphoacylglycerols have f.acids as part of their
covalently bonded structures
 The bond between the f.acids and the rest of the molecule can be
hydrolyzed (as shown in the fig.)
Fig. 21-1, p.569

p.569

Fig. 21-3, p.570

• Fatty acids oxidation begins with activation of the molecule.
• A thioester bond is formed between carboxyl group of f.acid
and the thiol group of coenzyme A (CoA-SH) (esterification
reaction – in cytosol)

Fig. 21-5, p.571

When a f.acid with an even number of C atoms undergoes
successive rounds of β-oxidation cycle, the product is acetyl-
CoA.
No. of molecules of acetyl-CoA produced = ½ the no. of C
atoms in the original f.acid. (as shown in fig above)
The acetyl-CoA enters the TCA cycle (the rest of oxidation to
CO2 and H2O taking place via TCA cycle and ETC)
β-oxidation takes place in mitochondria.

The oxidation of
unsaturated
f.acids does not
generate as many
ATPs as it would
for a saturated
f.acids (same C
atoms) – the
presence of
double bond
• the acyl-deH2ase
step skipped –
fewer FADH2 will
be produced

The catabolism of odd-carbon f.acids

Ketone bodies
Substances related to acetone (“ketone bodies”) are
produced when an excess of acetyl-CoA arises from β-
oxidation
Occurs because when there are not enough OAA to
react with acetyl-CoA in TCA cycle
When organisms has a high intake of lipids and low
intake of CHO or starvation and diabetes
The reactions that result in ketone bodies start with the
condensation of two molecules of acetyl-CoA to
produce acetoacetyl-CoA

• the odor of acetone can be detected on the
breath of diabetics whose not controlled by
suitable treatment
• Acetoacetate and β-hydroxybutyrate are acidic,
their presence at high [ ] overwhelms the
buffering capacity of the blood
• to lowered the blood pH is dealt by excreting
H+ into the urine, accompanied by excretion of
Na +, K + and water → results in severe
dehydration and diabetic coma
• synthesis of ketone bodies in liver mitochondria
• transport ketone bodies in the bloodstream;
water soluble
• other organs such as heart muscle and renal
cortex can use ketone bodies (acetoacetate) as the
preferred source of energy
• even in brain, starvation conditions lead to the
use of acetoacetate for energy

FATTY ACID SYNTHESIS
 The anabolic reaction takes place in cytosol
 Important features of pathway:
Intermediates are bound to sulfhydral groups of acyl carrier protein
(ACP); intermediates of β-oxidation are bonded to CoA
 Growing fatty acid chain is elongated by sequential addition of two-
carbon units derived from acetyl CoA
 Reducing power comes from NADPH; oxidants in β-oxidation are
NAD+ and FAD
 Elongation of fatty acid stops when palmitate (C 16) is formed;
further elongation and insertion of double bonds carried out later
by other enzymes

Pathway of palmitate
synthesis from
acetyl-CoA and
malonyl-CoA
The biosynthesis of
f.acids involves the
successive addition of
two-carbon units to
the growing chain.
- Two of the three C
atoms of the malonyl
group of malonyl-
CoA are added to the
growing fatty-acid
chain with each cycle
of the biosynthetic
reaction

This reaction require multienzyme complex :
fatty acid synthase
Fig. 21-15c, p.583

Fig. 21-17, p.586

 Lipids are transported throughout the body as lipoproteins
 Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids and contain cell-
targeting signals.
 Lipoproteins classified according to their densities:
 chylomicrons - contain dietary triacylglycerols
 chylomicron remnants - contain dietary cholesterol esters
 very low density lipoproteins (VLDLs) - transport endogenous triacylglycerols, which are
hydrolyzed by lipoprotein lipase at capillary surface
 intermediate-density lipoproteins (IDL) - contain endogenous cholesterol esters, which are taken
up by liver cells via receptor-mediated endocytosis and converted to LDLs
 low-density lipoproteins (LDL) - contain endogenous cholesterol esters, which are taken up by
liver cells via receptor-mediated endocytosis; major carrier of cholesterol in blood; regulates de
novo cholesterol synthesis at level of target cell
 high-density lipoproteins - contain endogenous cholesterol esters released from dying cells and
membranes undergoing turnover