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