beta oxidation part ii
DESCRIPTION
Beta Oxidation Part II. 3 Obstacles. Unsaturated fatty acid. Obstacle of cis double bonds. Polyunsaturated fatty acid. Obstacle of position of double bond. Odd number chain fatty acid. Obstacle of 3 carbons at the end. H. H. C=C. - PowerPoint PPT PresentationTRANSCRIPT
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