Beta Oxidation Part II

Unsaturated fatty acid

Polyunsaturated fatty acid

Odd number chain fatty acid

Obstacle of cis double bonds

Obstacle of position of double bond

Obstacle of 3 carbons at the end

3 Obstacles

CH3CH2CH2CH2CH2C CH2CH2CH2CH2CH2CH2CH2CO~SCoAC=C

HH4 3 2 1

Whoops!A cis D.B. will interfere

Oleic Acid

CH3CH2CH2CH2 CH2 CH2CH2CH2CH2CH2CH2CH2CO~SCoAC=C

HHC=C

HH12345

Linoleic

C18:cis9

Unsaturated and Polyunsaturated Require Additional Enzymes

H H

CH3CH2CH2

C=CCH2CH2CH2-CO~SCoA

Cleavage here

New COO group

New carbon

8 7

CH3CH2CH2

CH2C C-CO~SCoA

H

H

8 7

Enoyl CoAIsomerase

9

9

Trans double bond

CH2-CH2

C=C

CH2

C=C

CH2-CH2-CH2-CH2-CH2-CH2CH2C~SCoA

O

H 9HHH

O

CH2C~SCoA

O

CH2C~SCoAO

CH2C~SCoA

1234

O

CH3C~SCoA12

O

CH3C~SCoA34

O

CH3C~SCoA56

Linoleic Acid C18 cis 9,12

Poly Unsaturated (Continued)

9

-CH2 CH2 CH2CO~SCoAC=CH H

C=CH H

-CH2 CH2 C-CO~SCoAC-CH H

C=CH H

H

-CH2 CH2

CH2CO~SCoAC=CH H

Enoyl-CoAisomerase

Round 5starter

Round 4starter

Beta carbon to be

Text 641

Round 5starter

FADH2

FAD

CO~SCoAC=CH H

CH2

Dead end

Acyl-CoAdehydrogenase

Acyl-CoAdehydrogenase

-CH2 CH2

CH2CO~SCoAC=CH H

New Strategy

C-CO~SCoAC

C=CH H

H

H

beta 6

NADP+

NADPH + H+

2,4 dienoyl-CoAreductase

2,4 dienoyl-CoAreductase

3,2 enoyl-CoAisomerase

3,2 enoyl-CoAisomerase

CH2CO~SCoA H

CCCH2

H

Continue Beta Oxidation

Reduce near (bond), Shift far (bond)

C-CO~SCoAC

C=CH H

H

H

beta 6

beta 6

H

C-CO~SCoA C

CH2-CH2

H

beta 6

CH3CH2CH2CH2CH2CH2CO~SCoA

ODD CHAIN

One-carbon release prohibited

CH3CH2CO~SCoAPropionyl CoA

CH2

CH2

CO~SCoA

COO-Succinyl-CoA

Nature’s Folly Pathway

C-C-C~SCoA

C-C-C~SCoA

C-C-C~SCoA

CO2

WHOOPS!Wrong side

CO2

Put it here Dummy

To get the COO- on the end:

C-C-CO~SCoACO2

1

2

2. Move the big bulky CoA group to the end carbon

C-CCoAS~OC-

CO2

1. Move the tiny COO- group to the end carbon

The big bulky CoAGroup is moved

Succinyl CoA

OOC-C C-H

C

O

CoAS H

H H

OOC-C C-H

C

O

SCoA H

H HMethylmalonyl- CoA mutase

1, 2 Shift Catalyzed by Vitamin B12 with Cobalt

Vicinal groups on adjoining carbons, one with H

Free radical intermediate associated with Cobalt II

Homolytic cleavage (bonding electrons split evenly)

Abstracts a hydrogen atom from 5’-deoxyadenosyl group

Causes rearrangement

See p644-645See p644-645

Never sets free any of the components

Methylmalonic acid in urine is a sign of vitamin B12 deficiency

N

NN

N

CO

NH

H3C-CH

PO

O

N

N

CH3

CH3

O

C

CH

C

CH3

CH3

CH3

CH3R'

R'

R'

H

R

H

H

R

R

H3C

H

H3C

Co+

CN

CH2

CH2

CH2

OH

HOCH2

O

O

Vitamin B12

(cyano- cobalamin)

5’-deoxyadenosyl cobalamin

5’-deoxyadenosyl group

H-C-H

Co2+

R

ATP

PPPN

N N

N

OHOOH

H H

H H

CH2

OHOOH

H H

H H

N

N N

N

CH2

Co

PPP

3+

NH2

NH2

Mechanism of 1,2 Shift Catalyzed by Vitamin B12

Start here

homolytic cleavage

Carbohydrate and Fat Oxidation

Dr. Robert Atkins

Dogma: “Fats burn in the flame of carbohydrates”

1. CHO provide pyruvate

2. Pyruvate converted to OAA prompts citrate synthesis

4. Citrate is oxidized to CO2 and H2O

5. Ergo, carbohydrates aid in the oxidation of fat and prevent obesity caused by fat storage.

3. Citrate steers acetyl-CoA away from fat synthesis

Dr. Robert Atkins

“Carbohydrates don’t block fat storage,they promote it”

1. Carbohydrates raise blood glucose

2. Blood glucose triggers insulin

4. Malonyl-CoA, the product of ACC blocks carnitine-acyl transferase I, shutting down fatty acid import into mitochondria, stopping beta oxidation

3. Insulin activates acetyl-CoA carboxylase (ACC), a rate-controlling enzyme in fatty acid biosynthesis

5. ERGO: a meal rich in carbohydrate actually thwarts the oxidation of fatty acids and promotes fat synthesis and obesity