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CHAPTER 17: Fatty Acid Catabolism - Coggle Diagram
CHAPTER 17:
Fatty Acid Catabolism
Ketone
Formation of Ketone Bodies:
Degradation of HMG-CoA
In order to traffic to other tissues, CoA must be removed. Acetone, acetoacetate, and β-hydroxybutyrate can then travel through the blood.
Acetone is removed as a gas and exhaled, but acetoacetate and β-hydroxybutyrate can traffic to the brain for use in energy production.
The Liver Is the Source of Ketone Bodies
Formation of Ketone Bodies:
Generating Free CoA
The first step is reverse of the last step in the β oxidation: thiolase reaction joins two acetate units.
A third acetyl-CoA is incorporated in the second step.
Together, two CoA are freed from three acetyl- CoA.
Ketone Bodies as Fuel
Ketone Bodies
Entry of acetyl-CoA into citric acid cycle requires oxaloacetate.
When oxaloacetate is depleted, acetyl-CoA is converted into ketone bodies.
– frees coenzyme A for continued β oxidation
Three forms of ketone bodies can leave the liver: acetone, acetoacetate, and β - hydroxybutyrate.
基本知識
Oxidation of Fatty Acids Is a Major
Energy Source in Many Organisms
About one-third of our energy needs comes from dietary triacylglycerols.
About 80% of energy needs of mammalian heart and liver are met by oxidation of fatty acids.
Many hibernating animals, such as grizzly bears, rely almost exclusively on fats as their source of energy.
Fats Provide Efficient Fuel Storage
The advantage of fats
over polysaccharides:
Fatty acids carry more energy per carbon because they are
more reduced.
Fatty acids complex or carry less water because they are
nonpolar.
Glucose and glycogen are for short-term energy needs and quick delivery.
Fats are for long-term (months) energy needs, good storage, and slow delivery.
Oxidation of Unsaturated Fatty Acids
Oxidation of Odd-Numbered Fatty Acids
Most dietary fatty acids are even-numbered.
Many plants and some marine organisms also synthesize odd-numbered fatty acids.
Propionyl-CoA (3-carbon compound) forms during 39 final cycle of β oxidation of odd-numbered fatty acids.
Bacterial metabolism in the rumen of ruminants also produces propionyl-CoA.
Oxidation of Propionyl-CoA
Polyunsaturated
Carboxylation of Propionyl-CoA
Monounsaturated
Isomerization to Succinyl-CoA => CAC
基本
Naturally occurring unsaturated fatty acids contain cis double bonds.
– are NOT a substrate for enoyl-CoA hydratase
Two additional enzymes are required.
– isomerase: converts cis double bonds starting at carbon 3 to trans double bonds
– reductase: reduces cis double bonds not at carbon 3
Monounsaturated fatty acids require the isomerase.
Polyunsaturated fatty acids require both enzymes.
Isomerization in Propionate Oxidation Requires Coenzyme B12
Complex Cobalt-Containing Compound: Coenzyme B12
Transport
Lipases Cleave Fatty Acids from Glycerol Backbone of Triacylglycerides
Glycerol from Fats Enters Glycolysis
Glycerol kinase activates glycerol at the expense of ATP.
Subsequent reactions recover more than enough ATP to cover this cost.
Allows limited anaerobic catabolism of fats
Hormones Trigger Mobilization of Stored Triacylglycerols
Transport or Attachment to Phospholipids Requires Conversion to Fatty Acyl-CoA
Lipids Are Transported in the Blood as Chylomicrons
Fatty Acid Transport into Mitochondria
Fats are degraded into fatty acids and glycerol in the cytoplasm of adipocytes.
Fatty acids are transported to other tissues for fuel through the blood.
β oxidation of fatty acids occurs in mitochondria.
Small (< 12 carbons) fatty acids diffuse freely across mitochondrial membranes.
Larger fatty acids (most free fatty acids) are transported via acyl-carnitine/carnitine transporter.
Dietary Fatty Acids Are Absorbed in the Vertebrate Small Intestine
Acyl-Carnitine/Carnitine Transport
Fatty Acid Oxidation
Stages
Stage 1 consists of oxidative conversion of two-carbon units into acetyl-CoA via β oxidation with concomitant generation of NADH and FADH2.
– involves oxidation of carbon to thioester of fatty acyl-CoA
Stage 2 involves oxidation of acetyl-CoA into CO2 via citric acid cycle with concomitant generation NADH and FADH 2.
Stage 3 generates ATP from NADH and FADH2 via the respiratory chain.
β -Oxidation
Fatty Acid Oxidation is Performed by a
Single Trifunctional Protein
Hetero-octamer
four α subunits
enoyl-CoA hydratase activity
β-hydroxyacyl-CoA dehydrogenase activity
responsible for binding to membrane
four β subunits
long-chain thiolase activity
May allow substrate channeling between enzymes
Associated with inner-mitochondrial membrane
Processes fatty acid chains with 12 or more carbons
Shorter chains processed by soluble enzymes in the matrix
Each Round Produces an Acetyl-CoA and Shortens the Chain by Two Carbons
Fatty Acid Catabolism for Energy
For palmitic acid (C16)– Repeating the previous four-step process six more times (seven total) results in eight molecules of acetyl-CoA.
• FADH2 is formed in each cycle (seven total).
• NADH is formed in each cycle (seven total).
Acetyl-CoA enters citric acid cycle and further oxidizes into CO2.
– This makes more GTP, NADH, and FADH2.
Electrons from all FADH2 and NADH enter ETF.
NADH and FADH2 Serve as Sources of ATP
Similar Mechanisms Introduce Carbonyls
in Other Metabolic Pathways