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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.
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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 CH3CH2CH2CH2CH2C CH2CH2CH2CH2CH2CH2CH2CO~SCoA Whoops! 4 2 3 4 1 1 2 3 5 H H H H C=C C=C CH3CH2CH2CH2 CH2 CH2CH2CH2CH2CH2CH2CH2CO~SCoA Oleic Acid C18:cis9 A cis D.B. will interfere Linoleic
New carbon Cleavage here 9 H H C=C CH3CH2CH2 CH2CH2CH2-CO~SCoA New COO group 9 H 8 7 CH2C CH3CH2CH2 C-CO~SCoA H Unsaturated and Polyunsaturated Require Additional Enzymes 8 7 Enoyl CoA Isomerase Trans double bond
H H H H 9 C=C C=C CH2-CH2 CH2 CH2-CH2-CH2-CH2-CH2-CH2CH2C~SCoA O CH3C~SCoA CH3C~SCoA CH3C~SCoA CH2C~SCoA CH2C~SCoA CH2C~SCoA O O O O O O 6 5 4 3 2 1 4 1 3 2 Linoleic Acid C18 cis9,12
9 -CH2 CH2 CH2CO~SCoA -CH2 CH2 -CH2 CH2 C-CO~SCoA H H H H H H H H H H C=C C=C CH2CO~SCoA C=C C=C C-C H Round 4 starter Round 5 starter Beta carbon to be Poly Unsaturated (Continued) Enoyl-CoA isomerase
beta 6 -CH2 CH2 H FAD H H H H H H C=C CH2CO~SCoA C=C C-CO~SCoA C=C H FADH2 C Round 5 starter CO~SCoA CH2 Dead end Acyl-CoA dehydrogenase New Strategy Text 641
H beta 6 H CH2 C CH2CO~SCoA NADPH + H+ C H H NADP+ H C=C C-CO~SCoA H beta 6 beta 6 H -CH2 CH2 C-CO~SCoA C C H Reduce near (bond), Shift far (bond) 2,4 dienoyl-CoA reductase 3,2 enoyl-CoA isomerase Continue Beta Oxidation
CO~SCoA CH2 CH2 COO- ODD CHAIN CH3CH2CH2CH2CH2CH2CO~SCoA One-carbon release prohibited CH3CH2CO~SCoA Propionyl CoA Succinyl-CoA
Put it here Dummy CO2 CO2 Nature’s Folly Pathway C-C-C~SCoA C-C-C~SCoA WHOOPS! Wrong side C-C-C~SCoA
2 C-C-CO~SCoA CO2 1 CoAS~OC- C-C CO2 To get the COO- on the end: 1. Move the tiny COO- group to the end carbon 2. Move the big bulky CoA group to the end carbon The big bulky CoA Group is moved Succinyl CoA
H H H H OOC-C C-H OOC-C C-H H H CoAS C O SCoA C O 1, 2 Shift Catalyzed by Vitamin B12 with Cobalt See p644-645 Methylmalonyl- CoA mutase Vicinal groups on adjoining carbons, one with H Homolytic cleavage (bonding electrons split evenly) Free radical intermediate associated with Cobalt II Abstracts a hydrogen atom from 5’-deoxyadenosyl group Causes rearrangement Never sets free any of the components Methylmalonic acid in urine is a sign of vitamin B12 deficiency
N N CH2 N N N N PPP N N NH2 PPP H H H H O O OH OH HO HO R H H H H H-C-H CH2 3+ 2+ Co Co NH2 Vitamin B12 ATP (cyano- cobalamin) 5’-deoxyadenosyl cobalamin 5’-deoxyadenosyl group
Mechanism of 1,2 Shift Catalyzed by Vitamin B12 Start here homolytic cleavage
Carbohydrate and Fat Oxidation Dogma: “Fats burn in the flame of carbohydrates” 1. CHO provide pyruvate Dr. Robert Atkins 2. Pyruvate converted to OAA prompts citrate synthesis 3. Citrate steers acetyl-CoA away from fat 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.
“Carbohydrates don’t block fat storage, they promote it” 1. Carbohydrates raise blood glucose 2. Blood glucose triggers insulin Dr. Robert Atkins 3. Insulin activates acetyl-CoA carboxylase (ACC), a rate- controlling enzyme in fatty acid biosynthesis 4. Malonyl-CoA, the product of ACC blocks carnitine-acyl transferase I, shutting down fatty acid import into mitochondria, stopping beta oxidation 5. ERGO: a meal rich in carbohydrate actually thwarts the oxidation of fatty acids and promotes fat synthesis and obesity
