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

CH 3 CH 2 CH 2 CH 2 CH 2 C CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CO~SCoA C=C H H 4321 Whoops! A cis D.B. will interfere Oleic Acid CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CO~SCoA C=C H H H H Linoleic C18:cis  9

Unsaturated and Polyunsaturated Require Additional Enzymes HH CH 3 CH 2 CH 2 C=C CH 2 CH 2 CH 2 -CO~SCoA Cleavage here New COO group New  carbon 87 CH 3 CH 2 CH 2 CH 2 C C-CO~SCoA H H 87 Enoyl CoA Isomerase 9 9 Trans double bond

CH 2 -CH 2 C=C CH 2 C=C CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 CH 2 C~SCoA O H 9 H HH O CH 2 C~SCoA O O O CH 3 C~SCoA 12 O 34 O 56 Linoleic Acid C18 cis  9,12

Poly Unsaturated (Continued) 9 -CH 2 CH 2 CH 2 CO~SCoA C=C H H H H -CH 2 CH 2 C-CO~SCoA C-C H H C=C H H H -CH 2 CH 2 CH 2 CO~SCoAC=C H H Enoyl-CoA isomerase Round 5 starter Round 4 starter Beta carbon to be

Text 641 Round 5 starter FADH 2 FAD CO~SCoA C=C H H CH 2 Dead end Acyl-CoA dehydrogenase Acyl-CoA dehydrogenase -CH 2 CH 2 CH 2 CO~SCoAC=C H H New Strategy C-CO~SCoA C C=C H H H H beta 6

NADP+ NADPH + H + 2,4 dienoyl-CoA reductase 2,4 dienoyl-CoA reductase 3,2 enoyl-CoA isomerase 3,2 enoyl-CoA isomerase CH 2 CO~SCoA H C CCH 2 H Continue Beta Oxidation Reduce near (bond), Shift far (bond) C-CO~SCoA C C=C H H H H beta 6 H C-CO~SCoA C CH 2 -CH 2 H beta 6

CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CO~SCoA ODD CHAIN  One-carbon release prohibited CH 3 CH 2 CO~SCoA Propionyl CoA CH 2 CO~SCoA COO - Succinyl-CoA

Nature’s Folly Pathway C-C-C~SCoA CO 2 WHOOPS! Wrong side CO 2 Put it here Dummy

To get the COO - on the end: C-C-CO~SCoA CO Move the big bulky CoA group to the end carbon C-CCoAS~OC- CO 2 1. Move the tiny COO - group to the end carbon The big bulky CoA Group is moved Succinyl CoA

OOC-C C-H C O CoAS H H H OOC-C C-H C O SCoA H H H Methylmalonyl- CoA mutase 1, 2 Shift Catalyzed by Vitamin B 12 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 p Never sets free any of the components Methylmalonic acid in urine is a sign of vitamin B 12 deficiency

Vitamin B 12 (cyano- cobalamin) 5’-deoxyadenosyl cobalamin 5’-deoxyadenosyl group H-C-H Co 2+ R ATP PPP N N N N O HOOH H H H H CH 2 O HOOH H H H H N N N N CH 2 Co PPP 3+ NH 2

Mechanism of 1,2 Shift Catalyzed by Vitamin B 12 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 CO 2 and H 2 O 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