![Page 1: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/1.jpg)
FattyAcidMetabolism
Dr.KevinAhern
![Page 2: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/2.jpg)
αβ
FattyAcidMetabolism• Fatty Acid Oxidation - Beta Oxidation
• Enzymes in Mitochondriaand Peroxisomes
• Generates More ATP Per Carbon Than Sugars
• Proceeds 2 Carbons at a Time
α-carbonβ-carbon
All Reactions Occur Between α and β Carbons
![Page 3: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/3.jpg)
FattyAcidMetabolism• Preparation for Oxidation
• Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion.
• Activation Begins in the Cytoplasm
Long Chain Fatty Acyl-CoA Ligase
Fatty Acid Fatty Acyl-CoA
![Page 4: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/4.jpg)
• To Move the Acyl-CoA into the Mitochondrion, the CoA is Swapped with a Molecule of Carnitine
![Page 5: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/5.jpg)
Four Steps in Fatty Acid Oxidation
![Page 6: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/6.jpg)
FattyAcidMetabolism• Beta Oxidation - Reaction 1
α
β
• Oxidation Creates Trans Intermediate • Unrelated to Trans fat • Three forms of Enzyme • Medium Form Problem in SIDS
Used to Generate ATP in Oxidative Phosphorylation
![Page 7: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/7.jpg)
FattyAcidMetabolism• Beta Oxidation Reaction 2
α
β
α
β
• Similar to Fumarase Reaction of Citric Acid Cycle • Preparation for Next Oxidation Step
![Page 8: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/8.jpg)
FattyAcidMetabolism• Beta Oxidation Reaction 3
α
β
α
β
• Similar to Malate Dehydrogenase Reaction of Citric Acid Cycle
Used to Generate ATP in Oxidative Phosphorylation
![Page 9: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/9.jpg)
FattyAcidMetabolism• Beta Oxidation Reaction 4
α
β
• Thiolase Enzyme Catalyzes the Reverse Reaction When the R-Group is a Hydrogen - Important for Ketone Body Synthesis
Shortened by 2 Carbons
Oxidized in Citric Acid Cycle
![Page 10: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/10.jpg)
FattyAcidMetabolism• Fatty Acid Oxidation - Summary
• In Summary - Each Round of Oxidation Creates One FADH2, One NADH, one Acetyl-CoA, and a Fatty Acid Shortened by Two Carbons
• Each Acetyl-CoA Released in Matrix of Mitochondrion Where it is Readily Oxidized in the Citric Acid Cycle.
![Page 11: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/11.jpg)
Similarity of Fatty Acid Oxidation and Citric Acid Cycle
![Page 12: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/12.jpg)
Unsaturated Fatty Acid Oxidation
![Page 13: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/13.jpg)
Unsaturated Fatty Acid Oxidation
1 23 4
![Page 14: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/14.jpg)
Unsaturated Fatty Acid Oxidation
1 23 4
12 3 4
![Page 15: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/15.jpg)
Unsaturated Fatty Acid Oxidation
1 2 3 4
![Page 16: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/16.jpg)
Unsaturated Fatty Acid Oxidation
![Page 17: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/17.jpg)
Unsaturated Fatty Acid Oxidation
![Page 18: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/18.jpg)
FattyAcidMetabolism• 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-CoA
![Page 19: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/19.jpg)
![Page 20: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/20.jpg)
Fatty Acid Synthesis vs Oxidation
Synt
hesi
s Oxidation
![Page 21: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/21.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis - Regulation
•Located in Cytoplasm •Feedback Inhibition by Long Chain Fatty Acids •Polymerization of Enzyme Favors Activation
![Page 22: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/22.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
•Remaining Catalysis Starting Here Occurs in Fatty Acid Synthase Complex
1. Replacement of CoA with Acyl Carrier Protein (ACP)
Malonyl-CoA Malonyl-ACP
ACP CoASH
Transacylase
Acetyl-CoA Acetyl-ACP
ACP CoASH
Transacylase
![Page 23: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/23.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
2. Joining of 2 Carbons from Malonyl-ACP to Growing Acyl Chain
3-Ketoacyl ACP Synthase
![Page 24: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/24.jpg)
3-Ketoacyl ACP Reductase
FattyAcidMetabolism• Fatty Acid Synthesis
3. Reduction of Ketone on Beta Carbon
OH is in D-Configuration, in Contrast to L-Form in Beta Oxidation
![Page 25: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/25.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
4. Removal of Water, Creating a Trans Double Bond
3-Hydroxyacyl ACP Dehydrase
![Page 26: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/26.jpg)
Enoyl ACP Reductase
FattyAcidMetabolism• Fatty Acid Synthesis
5. Reduction of Double Bond
Cycle of 2 Carbon Additions Continues Until 16 Carbons Reached - Palmitic Acid
Fatty Acid has Grown by 2 Carbons and Becomes Template for Next Cycle
![Page 27: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/27.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
6. Release of Palmitic Acid at End of Cycle
Palmitoyl-ACP
Palmitic Acid
ACP
Thioesterase
![Page 28: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/28.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
1. Replacement of CoA with Acyl Carrier Protein (ACP)
![Page 29: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/29.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
2. Joining of 2 Carbons from Malonyl-ACP to Growing Acyl Chain
![Page 30: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/30.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
3. Reduction of Ketone on Beta Carbon
![Page 31: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/31.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
4. Removal of Water, Creating a Trans Double Bond
![Page 32: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/32.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
5. Reduction of Double Bond
![Page 33: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/33.jpg)
FattyAcidMetabolism• Fatty Acid Synthesis
6. Release of Palmitic Acid at End of Cycle
![Page 34: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/34.jpg)
FattyAcidMetabolism• 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
![Page 35: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/35.jpg)
![Page 36: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/36.jpg)
Prostagen, Thromboxane, and Leukotriene Synthesis
Common Location of Arachidonic Acid
![Page 37: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/37.jpg)
Prostagen, Thromboxane, and Leukotriene Synthesis
![Page 38: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/38.jpg)
Synthesis of Some Prostaglandins
![Page 39: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/39.jpg)
![Page 40: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/40.jpg)
![Page 41: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/41.jpg)
Females
Males
Obesity
![Page 42: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/42.jpg)
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
![Page 43: Fatty Acid Metabolism - Oregon State UniversityFatty Acid Metabolism • Preparation for Oxidation •Before Oxidation, Fatty Acids Must be Activated and Transported to the Mitochondrion](https://reader033.vdocuments.pub/reader033/viewer/2022053106/606ff9bcbd5c0d69301096c7/html5/thumbnails/43.jpg)
The mouse on the left is deficient in leptin