Objectives

By the end of lecture the student should:

Discuss β oxidation of fatty acids.

Illustrate α oxidation of fatty acids.

Understand ω oxidation of fatty acids.

List sources and fates of active acetate.

Oxidation of Fatty Acids

1- β-Oxidation (knoop’s oxidation):

Removal of 2 carbon fragment at a time form

Acyl CoA (active FA).

The 2 carbon removed as acetyl CoA.

It occurs in many tissues including liver,

kidney & heart

FAs to be oxidized must be entered the following 2 steps

1-Activation of FA 2- Transport of acyl

COA to mitochondria

RCOOH Acyl COA synthetase

RCO~SCOA

AMP+P~P COASH

2Pi + E

Pyrophosphatase

1-FA activation

ATP

2- Transport of acyl COA to mitochondria:

Role of carnitine in the transport of LCFA through the inner mithochochondrial membrane

1- Transport long chain acyl COA across mitochondrial

membrane into the mitochondria so it increases the rate

of oxidation of LCFA

2- Transport acetyl-CoA from mitochondria to cytoplasm

So it stimulates fatty acid synthesis

Functions of carnitine

α

Cβ

O ~ S – CoA β

H3C

Palmitoyl-CoA

CoA-SH

α

CO ~ S – CoA β

H3C

Successive removal of C2 units

CO ~ S – CoA

Acetyl-CoA

+

8CH3 – CO ~ S – CoA

Acetyl-CoA

CoA-SH

β

Palmitoyl-CoA

α

β

H3C

H3C

α

CH3 – CO ~ S –CoA

+ β

8CH3 – CO ~ S – CoA

Acetyl-CoA

Steps of β-Oxidation of

FAs

Energetics of FA oxidation

Palmitic (16C):

β-oxidation of palmitic acid will be repeated 7

cycles producing 8 molecules of acetyl COA

In each cycle FADH2 and NADH+H+ is

produced & transported to respiratory chain

FADH2 ------------------ 2 ATP

NADH+H+ ------------- 3 ATP

So 7 cycles 5X7=35 ATP

each acetyl-CoA which is oxidized in citric

cycle gives 12 ATP (8X 12= 96 ATP)

2 ATP is utilized in the activation of fatty acid

(it occurs once)

Energy gain = Energy produced-Energy utilized

= 35 ATP+ 96 ATP-2 ATP= 129 ATP

Calculation of Energetics of any FA Oxidation:

[(N/2-1)X 5 ATP]+[N/2X12 ATP]-2ATP

(N= Number of carbons of fatty acid)

This type of oxidation occurs in α

position with the removal of one carbon

from the carboxyl end of fatty acids.

Site: microsomes of

brain

liver tissues

Does not require coenzyme A & does

not generate ATP.

2- α – Oxidation

CH3

R.CH2 – CH – CH2 – COOH

Even long chain FA

O2

Hydroxylase

NADH+H+ NAD

α hydroxyl FA

CH3 OH

R.CH2 – CH – CH– COOH

NAD

NADH+H+

L ascorbic acid

CH3 O

R.CH2 – CH – C– COOH

α Keto FA

CO2 ½ O2

Odd long chain FA

CH3

R.CH2 – CH – COOH β oxidation

H2O

Mechanism

Functions:

1- Formation of α hydroxyl fatty acids which is a

constituent of brain lipids

2- Modification of FA with methyl groups on the β

carbon which block β oxidation e.g. phytanic acid

present in certain plants, it has 4 CH3 groups at

position 3, 7, 11, 15, by initial α oxidation &

removal of one carbon, CH3 groups is at α

position, FA undergo β oxidation

•rare neurological disorder

• caused by accumulation of phytanic

acid, a constituent of chlorophyll found in

plant foodstuffs

• Phytanic acid contains a CH3 gp on C3

that block β oxidation. SO an initial α

oxidation required to remove CH3 group

•Pathology

inherited defect in α oxidation leads to

accumulation of phynatic acid

Refsum’s disease

3- Omega Oxidation

• Occurs at terminal methyl group dicarboxylic

acid (HOOC R COOH)

• Site: microsomes of the liver

CH3 – R – COOH

O2

Cyt P450

NADH+H+ NADP

OH – CH2 – R– COOH

HOOC – CH2– COOH

Dicarboxylic acid In both sides

β oxidation

Cyt P450 H2O

3- Omega Oxidation

•The dicarboxylic acid formed may be shorted from both

ends by β oxidation 2 molecules of acetyl COA

each time

• Oxidation continues usually to adipic (C6) & suberic

(C6) acids which are excreted in urine

1- Carbohydrates: Glucose undergoes glycolysis forming pyruvic acid,

which enters the mitochondria where it undergoes oxidation decarboxylation to form acetyl-CoA

2- Fats: Fats are hydrolysed into glycerol and FA • Glycerol joins glycolysis at the step of dihydroxy

acetone phospate pyruvic acid acetyl – CoA • The fatty acid undergoes β – oxidation acetyl –

CoA

Of active acetate (acetyl COA)

3-Proteins:

Proteins are hydrolyzed to amino acids:

• The ketogenic amino acids form acetyl- CoA directly

or through the formation of aceto acetate

• The glucogenic amino acids first form pyruvate

either directly or through the formation of Kreb’s

cycle intermediates

Fate of acetyl CoA

1- Oxidation: Acetyl-CoA + oxalacetate citrate enter

the Kreb’s cycle CO2 + water + 12 ATP 2- Formation of Fatty Acids (lipogenesis): The excess acetyl-CoA resulting from the

oxidation of carbohydrates, or less commonly proteins, may be converted into fatty acids

3- Formation of Ketone Bodies: The excess acetyl-CoA resulting from oxidation of FA

in the liver may form ketone bodies (ketogenesis) 4- Formation of Steroids: Acetyl-CoA cholesterol steroid hormones,

bile acids & vitamin D3 5- Acetylation of Some Compunds: Acetyl-CoA is used for the acetylation of choline,

glucosamine and aromatic amines

Summary

Questions