objectives - mans...oxidation of fatty acids 1- β-oxidation (knoop’s oxidation): removal of 2...
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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.
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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
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FAs to be oxidized must be entered the following 2 steps
1-Activation of FA 2- Transport of acyl
COA to mitochondria
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RCOOH Acyl COA synthetase
RCO~SCOA
AMP+P~P COASH
2Pi + E
Pyrophosphatase
1-FA activation
ATP
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2- Transport of acyl COA to mitochondria:
Role of carnitine in the transport of LCFA through the inner mithochochondrial membrane
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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
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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
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Steps of β-Oxidation of
FAs
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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
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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)
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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
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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
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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
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•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
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3- Omega Oxidation
• Occurs at terminal methyl group dicarboxylic
acid (HOOC R COOH)
• Site: microsomes of the liver
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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
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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
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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)
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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
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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
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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
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Summary
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Questions
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