beta oxidation part i the break down of a fatty acid to acetyl-coa units…the ‘glycolysis’ of...
TRANSCRIPT
Beta Oxidation Part IThe break down of a fatty acid to acetyl-CoA
units…the ‘glycolysis’ of fatty acids
Occurs in the mitochondria
Exemplifies Aerobic Metabolism
at its most powerful phase
STRICTLY AEROBIC
Acetyl-CoA is fed directly into the Krebs cycle
Overproduction causes KETOSIS
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
Fatty Acid OxidationFatty Acid Oxidation
CH3CH2CH2COOH
[CH3CH2CH2CO-AMP]
CH3CH2CH2CO~SCoA
HS-CoA
Fatty acyl CoA
ATP
PPi
AMPFatty acylCoA Ligase
Prepares a Fatty Acid for transport and metabolism
Transport into Mitochondria depends on Carnitine
FA~CoA
FA~Carnitine
Acyl transferase I
FA~Carnitine Carnitine
Acyl transferase II
Translocase
HS-CoA
FA~CoA
HS-CoA
Carnitine
N(CH3)3
CH2
H-C-OH
COO-
CH2
+
Carnitine
CH3CH2CH2CH2CH2CH2CH2C~SCoAO
CH3C~SCoAO
CH3C~SCoAO
CH3C~SCoAO
CH3C~SCoAO
Beta Oxidation
8 carbon Fatty Acid Acyl-CoA
4 two carbon Acetyl-CoAs
CH2CH2CH2COO CH2CH2COO
OCH2CO COO
Diet
Urine
(even chain) (odd chain)
Phenylpyruvate Benzoate
Knoop’s Experiment
Phenylacetate Benzoate
C H2 C H 2 C H 2 C O O C H 2 C H 2 C O O
C H 2 C C C O O
H
HH
H
C H 2 C C C O O
H
H
C H 2 C C C O O
H
H H
HO
C H 2 C C C O O
H
H
O
B E TA OX ID ATIO N
Round
Dehydrogenase
Hydratase
Dehydrogenase
Acyl Transferase
FAD
H2O
NAD+
CH3CH2CH2CH2CH2CH2CH2C~S-CoAO
-C=C-C~S-CoAH
H O
-C- CH2-C~S-CoA
O O
-C- CH2-C~S-CoAO
H
H
O
-C…...CH3-C~S-CoA
O O
R
S-CoA
MECHANISM
TRANS
L-
Cofactor or Substrate
HS-CoA
Trans L Vania
When you think of beta oxidation
C6H12O6 + 6O2 6CO2 + 6H2O Ho = -2,813 kJ/mol = - 672 Cal/mol = 3.74 Cal/gram
C18H36O2 + 26O2 18CO2 + 18 H2O Ho = -11,441 kJ/mol = - 2,737 Cal/mol = 9.64 Cal/gram
THE ENERGY STORY PART I
Glucose
Stearic Acid
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)
Stearic Acid (C18 satd)
9 Acetyl CoA = 108 ATP (90)8 FADH2 = 16 ATP (24)
ENERGY CONSERVATION
8 NADH = 24 ATP (20)
= 148 ATP (134)- 1 ATP -1
147 ATP (133)
Textbook
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
Octoyl-CoA + 3HSCoA + 3FAD + 3NAD+ + 7H2O
CH3CH2 CH2CH2 CH2CH2 CH2CO~SCoA
HS-CoA
FADNAD+
4 Acetyl-CoA 40 ATP
R-1R-2R-3
C-8
3 FADH2 4.5 ATP
3 NADH + 3 H+ 7.5 ATP
52 ATP
HS-CoA
FADNAD+
HS-CoA
FADNAD+
CH3CH2 CH2CH2 CH2CH2 CH2CO~SCoA
CH3CH2 CH2CH2 CH2CO~SCoA
CH3CH2 CH2CO~SCoA
CH3CO~SCoA CH3CO~SCoA
FADNAD
HSCoA
FADNAD
HSCoA
FADNAD
HSCoA
123
Hexanoic acid (C6H12O2) Glucose (C6H12O6)
Hexanoic acid
Hexanoyl-CoA -1 ATP
Glucose
2 pyruvates 2 ATP
Hexanoyl-CoA
3 Acetyl-CoA 30 ATP2 pyruvates
2 Acetyl-CoA 20 ATP2 FADH2
3 ATP2 NADH + H+
2 NADH + H+ 5 ATP5 ATP
37 ATP32 ATP
2 NADH + H+ 5 ATP
Mwt = 116 Mwt = 180ATP per Gram = 0.32 ATP per Gram = 0.17