Download Beta Oxidation

Beta Oxidation Part I
The break down of a fatty acid to acetyl-CoA
units…the ‘glycolysis’ of fatty acids
STRICTLY AEROBIC
Occurs in the mitochondria
Acetyl-CoA is fed directly into the Krebs cycle
Overproduction causes KETOSIS
Exemplifies Aerobic Metabolism
at its most powerful phase
Fatty Acid Oxidation
Schedule of Topics
• Digestion, absorption and transport
• General mechanism of fatty acid
oxidation
• Oxidation of unsaturated fatty acids
• Odd chain fatty acids…role of
vitamin B12
• Ketone bodies and ketosis
CH3CH2CH2COOH
ATP
PPi
[CH3CH2CH2CO-AMP]
HS-CoA
AMP
Fatty acyl
CoA Ligase
CH3CH2CH2CO~SCoA
Fatty acyl CoA
Prepares a Fatty Acid for transport and metabolism
Transport into Mitochondria depends on Carnitine
+
FA~CoA
Acyl transferase I
N(CH3)3
CH2
HS-CoA
Carnitine
FA~Carnitine
H-C-OH
CH2
Translocase
FA~Carnitine
HS-CoA
FA~CoA
Carnitine
Acyl transferase II
COOCarnitine
Beta Oxidation
8 carbon Fatty Acid Acyl-CoA
CH3CH2CH2CH2CH2CH2CH2C~SCoA
O
CH3C~SCoA
O
CH3C~SCoA
O
CH3C~SCoA
O
CH3C~SCoA
O
4 two carbon Acetyl-CoAs
Knoop’s Experiment
Diet
(even chain)
(odd chain)
CH2CH2CH2COO
CH2CH2COO
Urine
CH2COO
Phenylpyruvate
Phenylacetate
COO
Benzoate
Benzoate
B E TA O X ID A TIO N
b
a
C H2C H2C H2C OO
H
C H2 C
H
H
b
C H2 C
b
a
b
C H2C H2C OO
H
a
C
C OO
H
a
C
C OO
H
H H
b
a
C H2 C C
C OO
HO H
H
b
a
C H2 C C
C OO
O H
MECHANISM
Round
b
CH3CH2CH2CH2CH2CH2CH2C~S-CoA
Cofactor or Substrate
O
H
Dehydrogenase -C=C-C~S-CoA
FAD
H O
TRANS
HO
Hydratase
-C- CH2-C~S-CoA
H2 O
H
LO
Dehydrogenase
Acyl
Transferase
-C- CH2-C~S-CoA
O
O
R -C…...CH3-C~S-CoA
O
O
S-CoA
NAD+
HS-CoA
Trans L Vania
When you think of
beta oxidation
THE ENERGY STORY
PART I
Glucose
C6H12O6 + 6O2  6CO2 + 6H2O Ho = -2,813 kJ/mol
= - 672 Cal/mol
= 3.74 Cal/gram
Stearic Acid
C18H36O2 + 26O2  18CO2 + 18 H2O Ho = -11,441 kJ/mol
= - 2,737 Cal/mol
= 9.64 Cal/gram
On a per mole basis a typical fatty acid is
4 times more energy rich that a typical hexose
Energy Story Part II
1.0 g glucose = 3.7 kcal (15.5 kJ)
1.0 g stearic acid = 9.7 kcal (40.5 kJ)
ENERGY CONSERVATION
Stearic Acid (C18 satd)
Textbook
9 Acetyl CoA
8 FADH2
= 108 ATP
= 16 ATP
(90)
(24)
8 NADH
= 24 ATP
(20)
= 148 ATP
- 1 ATP
(134)
-1
147 ATP
(133)
Palmitoyl-CoA (Textbook)
Palmitoyl-CoA + 7CoA + 7FAD + 7NAD+ + 7H2O
8 Acetyl-CoA
80 ATP
7 FADH2
10.5 ATP
7 NADH + 7H+
17.5 ATP
108 ATP
R-3
R-2
R-1
CH3CH2 CH2CH2 CH2CH2 CH2CO~SCoA
FAD
FAD
FAD
NAD+
NAD+
NAD+
HS-CoA HS-CoA HS-CoA
C-8
Octoyl-CoA + 3HSCoA + 3FAD + 3NAD+ + 7H2O
4 Acetyl-CoA
40 ATP
3 FADH2
4.5 ATP
3 NADH + 3 H+
7.5 ATP
52 ATP
b3
b2
b1
CH3CH2 CH2CH2 CH2CH2 CH2CO~SCoA
FAD
NAD
HSCoA
CH3CH2 CH2CH2 CH2CO~SCoA
FAD
NAD
HSCoA
CH3CH2 CH2CO~SCoA
FAD
NAD
HSCoA
CH3CO~SCoA
CH3CO~SCoA
Hexanoic acid (C6H12O2)
Hexanoic acid
Hexanoyl-CoA -1 ATP
Glucose (C6H12O6)
Glucose
2 pyruvates
2 ATP
2 NADH + H+ 5 ATP
Hexanoyl-CoA
3 Acetyl-CoA 30 ATP
2 pyruvates
2 Acetyl-CoA 20 ATP
2 FADH2
3 ATP
2 NADH + H+
5 ATP
37 ATP
Mwt = 116
ATP per Gram = 0.32
2 NADH + H+
5 ATP
32 ATP
Mwt = 180
ATP per Gram = 0.17