Fatty Acid Metabolism Biochemistry Free For All All

Fatty Acid Metabolism Biochemistry Free For All

All Reactions Occur Between α and β Carbons β-carbon Fatty Acid Metabolism • Fatty Acid Oxidation - Beta Oxidation • Enzymes in Mitochondria and Peroxisomes • Generates More ATP Per Carbon Than Sugars • Proceeds 2 Carbons at a Time β α α-carbon

Fatty Acid Metabolism • Preparation for Oxidation • Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion. • Activation Begins in the Cytoplasm Long Chain Fatty Acyl-Co. A Ligase Fatty Acid Fatty Acyl-Co. A

• To Move the Acyl-Co. A into the Mitochondrion, the Co. A is Swapped with a Molecule of Carnitine

Four Steps in Fatty Acid Oxidation

Fatty Acid Metabolism • Beta Oxidation - Reaction 1 • Oxidation Creates Trans Intermediate • Unrelated to Trans fat • Three forms of Enzyme • Medium Form Problem in SIDS Used to Generate ATP in Oxidative Phosphorylation β α

Fatty Acid Metabolism • Beta Oxidation Reaction 2 • Similar to Fumarase Reaction of Citric Acid Cycle • Preparation for Next Oxidation Step β β α α

Fatty Acid Metabolism • Beta Oxidation Reaction 3 • Similar to Malate Dehydrogenase Reaction of Citric Acid Cycle Used to Generate ATP in Oxidative Phosphorylation β β α α

Fatty Acid Metabolism • Beta Oxidation Reaction 4 • Thiolase Enzyme Catalyzes the Reverse Reaction When the R-Group is a Hydrogen - Important for Ketone Body Synthesis Oxidized in Citric Acid Cycle β α Shortened by 2 Carbons

Fatty Acid Metabolism • Fatty Acid Oxidation - Summary • In Summary - Each Round of Oxidation Creates One FADH 2, One NADH, one Acetyl-Co. A, and a Fatty Acid Shortened by Two Carbons • Each Acetyl-Co. A Released in Matrix of Mitochondrion Where it is Readily Oxidized in the Citric Acid Cycle.

Similarity of Fatty Acid Oxidation and Citric Acid Cycle

Unsaturated Fatty Acid Oxidation

Unsaturated Fatty Acid Oxidation 1 2 3 4

Unsaturated Fatty Acid Oxidation 1 2 3 4

Unsaturated Fatty Acid Oxidation 1 2 3 4

Unsaturated Fatty Acid Oxidation

Unsaturated Fatty Acid Oxidation

Fatty Acid Metabolism • Other Fatty Acid Oxidation 1. Long Chain Fatty Acids (20 -22 Carbons or Greater) are Oxidized in Beta Oxidation Reactions in Peroxisomes 2. Fatty Acids with Odd Numbers of Carbons and some Amino Acids are Oxidized in β-οxidation, Yielding Propionyl-Co. A

Oxidation Synthesis Fatty Acid Synthesis vs Oxidation

Fatty Acid Metabolism • Fatty Acid Synthesis - Regulation • Located in Cytoplasm • Feedback Inhibition by Long Chain Fatty Acids • Polymerization of Enzyme Favors Activation

Fatty Acid Metabolism • Fatty Acid Synthesis • Remaining Catalysis Starting Here Occurs in Fatty Acid Synthase Complex 1. Replacement of Co. A with Acyl Carrier Protein (ACP) ACP Co. ASH Transacylase Malonyl-Co. A Malonyl-ACP Co. ASH Transacylase Acetyl-Co. A Acetyl-ACP

Fatty Acid Metabolism • Fatty Acid Synthesis 2. Joining of 2 Carbons from Malonyl-ACP to Growing Acyl Chain 3 -Ketoacyl ACP Synthase

Fatty Acid Metabolism • Fatty Acid Synthesis 3. Reduction of Ketone on Beta Carbon OH is in D-Configuration, in Contrast to L-Form in Beta Oxidation 3 -Ketoacyl ACP Reductase

Fatty Acid Metabolism • Fatty Acid Synthesis 4. Removal of Water, Creating a Trans Double Bond 3 -Hydroxyacyl ACP Dehydrase

Fatty Acid Metabolism • Fatty Acid Synthesis 5. Reduction of Double Bond Fatty Acid has Grown by 2 Carbons and Becomes Template for Next Cycle Enoyl ACP Reductase Cycle of 2 Carbon Additions Continues Until 16 Carbons Reached - Palmitic Acid

Fatty Acid Metabolism • Fatty Acid Synthesis 6. Release of Palmitic Acid at End of Cycle Thioesterase Palmitic Acid ACP Palmitoyl-ACP

1. Replacement of Co. A with Acyl Carrier Protein (ACP) Fatty Acid Metabolism • Fatty Acid Synthesis

2. Joining of 2 Carbons from Malonyl-ACP to Growing Acyl Chain Fatty Acid Metabolism • Fatty Acid Synthesis

3. Reduction of Ketone on Beta Carbon Fatty Acid Metabolism • Fatty Acid Synthesis

4. Removal of Water, Creating a Trans Double Bond Fatty Acid Metabolism • Fatty Acid Synthesis

5. Reduction of Double Bond Fatty Acid Metabolism • Fatty Acid Synthesis

6. Release of Palmitic Acid at End of Cycle Fatty Acid Metabolism • Fatty Acid Synthesis

Fatty Acid Metabolism • Other Fatty Acid Syntheses 1. Fatty Acids Longer than 16 Carbons are Made in the Endoplasmic Reticulum and the Mitochondrion 2. Unsaturated Fatty Acids are Made by Desaturases Found in the Endoplasmic Reticulum 3. Linoleic Acid (double bonds at #9 & 12) and Linolenic Acid (double bonds at #9, 12, & 15) are Essential Fatty Acids in Humans Mammalian Desaturates Can’t Make Double Bonds Past Position Delta #9

Prostagen, Thromboxane, and Leukotriene Synthesis Common Location of Arachidonic Acid

Prostagen, Thromboxane, and Leukotriene Synthesis

Synthesis of Some Prostaglandins

Obesity Females Males

Obesity and Hunger Adipokines - Peptide Hormones in Adipocytes Leptin - Hunger suppressor Adiponectin - Regulate glucose levels, FA oxidation Resistin - Increased inflammation, insulin resistance Effects of leptin countered by ghrelin Leptin

The mouse on the left is deficient in leptin