O

||
CH2 - O - C - (CH2)n - CH3
O
||
CH - O - C - (CH2)n - CH3
O
||
CH2 - O - C - (CH2)n - CH3

Glycerol Fatty acid

Glycerol is converted to dihydroxyacetone phosphate,
by reactions catalyzed by:
1 Glycerol Kinase
2 Glycerol Phosphate Dehydrogenase.
Fatty acid oxidation occurs by removal of 2-C
units at a time with oxidation at the b-carbon
of the fatty acid
Fatty Acid b-Oxidation
Allcells except for RBCs and brain can use
fatty acids for energy.
b-Oxidation occurs in Mitochondria
Three Steps
A.activation
B.transport into mitochondria
C.oxidation
A.Fatty acid
activation

Acyl-CoA
Synthetase of
ER & outer
mitochondrial
membranes,
catalyzes fatty
acid activation
 fatty acid + ATP acyladenylate + PPi
PPi 2 Pi
acyladenylate + HS-CoA acyl-CoA + AMP

Overall:
fatty acid + ATP + HS-CoA acyl-CoA + AMP + 2 Pi

Exergonic hydrolysis of PPi (P~P), catalyzed

by Pyrophosphatase, makes the coupled
reaction spontaneous.
Fatty acids are linked to CoA in the cytosol.
Enzymes of the b-Oxidation Pathway are in the
mitochondrial matrix.
Transfer of the fatty acid across the inner
membrane involves carnitine
 The transfers long-chain fatty acyl CoA from the
cytosol into the mitochondria
Carnitine shuttle system
1.Acyl-CoA Dehydrogenase
catalyzes oxidation of the
fatty acyl-CoA, to form a
C2 to C3 double bond.
FAD is the e-
acceptor for Acyl-CoA
Dehydrogenase.
FADH2 is reoxidized
by transfer of 2 e- to
an electron transfer
flavoprotein (ETF),
which passes 2 e- to
coenzyme Q of the
respiratory chain.
2.Enoyl-CoA Hydratase
catalyzes hydration of the
trans double bond, yielding L-
hydroxyacyl-Coenzyme A.

3.Hydroxyacyl-CoA
Dehydrogenase
catalyzes oxidation of
the hydroxyl in the b
position (C3) to a ketone.
NAD+ is the electron
acceptor.

Process similar to
succinate oxidation in
the Citric Acid Cycle
(dehydrogenation,
hydration,
dehydrogenation)
4. b-Ketothiolase
catalyzes thiolytic
cleavage yielding fatty
acyl-CoA (2 C shorter)
and releasing Acetyl-CoA.
 The b oxidation
pathway is cyclic. The
product, 2 C shorter, is
the input to another
round of the pathway
Products: an acetyl-
CoA and a fatty acid
two carbons shorter,
FADH2, NADH
If the fatty acid
contains an even
number of C atoms,
Final cleavage product
is acetyl CoA.
If the number is
odd,final cleavage
product is propionyl
CoA
one round of the b-oxidation pathway:
fatty acyl-CoA + FAD + NAD+ + HS-CoA
fatty acyl-CoA (2 C less) + FADH2 + NADH
+ H+ + acetyl-CoA
Acetyl-CoA can enter Krebs cycle, yielding
additional NADH, FADH2, and GTP
 Getting Energy From
Food
Not responsible for:

Enzyme names and molecular

structures, (unless discussed
specifically in class

Details of metabolic pathways

15
 Complete b- oxidation of 1 mol
palmitic acid yields 106 mol ATP

How many cycles occurred in the oxidation of

palmitic acid? (#C/2) 1 (16/2) 1 =7
14 ATP per cycle 7 * 14 = 98
the last 2 carbons + 10
Subtrat 2 for the initial activation 2
Net ATP formed 106

Fatty acid oxidation is a major source of cell ATP

It also produces large amounts of metabolic
water( 130 H2O per palmitoyl-CoA).

The ship of the desert sails on its own metabolic

water.
 b-Oxidation of Unsaturated and
Odd Chain Fatty Acids

Variations on b-Oxidation - extra enzymes

required
Unsaturated FA (C18:1, C18:2, C18:3 and others)
require two extra enzymes to get double bonds in the right
place for enzymes of b-oxidation to workcis-trans isomerase,
reductase)
skip one or more oxidation steps -Slightly less Energy derived
as these molecules are slightly more oxidized to begin with
 b- Oxidation of Odd-Chain Fatty Acids

Odd-chain fatty acids occur in plants and

microorganisms
Final cleavage product is propionyl CoA
rather than acetyl CoA
Three enzymes convert propionyl CoA to
succinyl CoA (citric acid cycle intermediate)
Conversion of propionyl CoA to
succinyl CoA

Succinyl CoA --> oxalacetate--> glucose

(gluconeogenesis)
During CHO starvation, oxaloacetate in liver is depleted due to
gluconeogenesis. This impedes acetyl-CoA entry to Krebs cycle.
Acetyl-CoA in liver mitochondria is converted then to ketone
bodies.
 Acetone, Acetoacetate, - hydroxybutyrate
are called ketone bodies.
Produced in liver,Diffuse out of the liver into
the blood .Acetone is exhaled by the lungs,
Acetoacetate and beta hydroxybutyrate are
taken up by extrahepatic tissues and
catabolized for energy.
 Fuel molecules
derived from excess acetyl CoA
Water soluble
readily and quickly transported to
other tissues for energy
Majorsource of energy for brain in starvation
(skeletal muscle and kidney, also)
 Not exactly the reverse of degradation
by a different set of enzymes , in a different part of the
cell
Primarily in the cytoplasm of the following
tissues: liver, kidney, adipose, central
nervous system and lactating mammary gland
Rule: Fatty acid biosynthesis is a stepwise
assembly of acetyl-CoA units (mostly as
malonyl-CoA) ending with palmitate (C16
saturated)
3 Phase: Activation, Elongation, Termination
Liver is the major organ for fatty
acid synthesis
Synthesis Beta Oxidation

Cytosol Mitochondria
Requires NADPH NADH, FADH2
Acyl carrier protein CoA
D-isomer L-isomer
CO2 activation No CO2
Keto saturated Saturated keto
 O
O-C-R
O
R-C-O
O
O-C-R
Fatty acyl-CoA
DHAP reduction to glycerol-PO4
or
Glycerol kinase to glycerol-PO4
Two esterifications
Diacylglycerol-PO4 intermediate
Triacylglycerol
 80% in liver, ~10% intestine, ~5% skin
Occurs in cytosol

Requires 18Acetyl-CoA16NADPH36ATP

Similarto ketogenic pathway

Highly regulated
Cholesterol
Synthesis
Unsaturated
fatty acids
Synthesis
Synthesis of several prostaglandins from arachidonic acid