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Ch.17 Fatty Acid Catabolism - Coggle Diagram
Ch.17 Fatty Acid Catabolism
How fats are digested in animals
Fats Provide Efficient Fuel Storage
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.
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.
:star: Dietary Fatty Acids Are Absorbed in the Vertebrate Small Intestine
:one: bile salt emulsify :arrow_forward: mixed micelles
:two: intedtinal lipases degrade triacylglycerols
:three: breakdown products are taken by intestinal mucosa and converted to triacylglycerols
:four: forming chylomicrons (include triacylglycerols, cholesterol, apolipoproteins
:five: chylomicrons move through lymphatic system & bloodstream to tissue
:six: lipoprotein lipase (activated by apoC-2 in the capillary) convert triacylglycerols to fatty acid & glycerol
:seven: fatty acids enter cells :arrow_forward: oxidized as fuel or reesterfied for storage
How fats are mobilized and transported in tissues
Hormones Trigger Mobilization of Stored Triacylglycerols
:three: hormonesensitive lipase :arrow_forward: :five: adipose triacylglycerol lipase (ATGL) :arrow_forward: :eight: monoglycerol lipase (MGL)
perillipin :no_entry: ATGL
perillipin 磷酸化後離開CGI-58，接上ATGL :arrow_forward: 活化
Lipases are activated by hormones glucagon and epinepherine.
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
:star: Transport or Attachment to Phospholipids
Requires Conversion to Fatty AcyI-CoA
The carboxylate ion is adenylylated by ATP, to form a fatty acyl—adenylate and pm. The PPi is immediately hydrolyzed to two molecules Of Pi.
The CoA-SH attacks the acyl-adenylate (a mixed anhydride), displacing AMP a nd forming the thioester fatty a cyl—CoA.
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.
• "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.
:star:
How fats are oxidized
:star: Fatty Acid Oxidation Occurs in the
Mitochondria in Three Stages
• Stage 1 consists of oxidative conversion of two-carbon units into acetyl-CoA via [3 oxidation with concomitant generation of NADH and FADH2 — involves oxidation of ßcarbon to thioester of fatty acyl-CoA
• Stage 2 involves oxidation of acetyl-CoA into C02 via citric acid cycle with concomitant generation NADH and FADH2.
• Stage 3 generates ATP from NADH and FADH2 via the respiratory chain.
:star: Stages of Fatty Acid Oxidation
The β-Oxidation Pathway
:star:
Step 1:
Dehydrogenation of Alkane to Alkene
• Catalyzed by isoforms of acyl-CoA dehydrogenase (AD) on the inner-mitochondrial membrane
• Results in trans double bond, different from naturally occurring unsaturated fatty acids
• Analogous to succinate dehydrogenase reaction in the citric acid cycle — electrons from bound FAD transferred directly to the electron- transport chain via electron-transferring flavoprotein (ETF)
Step 2:
Hydration of Alkene
• Catalyzed by two isoforms of enoyl-CoA hydratase:
soluble short-chain hydratase (crotonase)
membrane-bound long-chain hydratase, part of trifunctional complex
• Water adds across the double bond yielding alcohol on "carbon.
• Analogous to fumarase reaction in the citric acid cycle
— same stereospecificity
Step 3:
Dehydrogenation of Alcohol
• Catalyzed by ß-hydroxyacyl-CoA dehydrogenase
• The enzyme uses NAD cofactor as the hydride acceptor.
• Only L-isomers of hydroxyacyl COA act as substrates.
• Analogous to malate dehydrogenase reaction in the citric acid cycle
Step 4:
Transfer of Fatty Acid Chain and Release of Acetyl-CoA
Catalyzed by acyl-CoA acetyltransferase (thiolase) via
covalent mechanism
Active-site thiolate acts as a nucleophile and releases acetyl-CoA.
Terminal sulfur in CoA-SH acts as a nucleophile and picks up the fatty acid chain from the enzyme.
The carbonyl carbon in ß-ketoacyl-CoA is electrophilic.
The net reaction is thiolysis of the carbon-carbon bond.
Each Round Produces an Acetyl-CoA &
Shortens the Chain by Two Carbons
Oxidation of Unsaturated Fatty Acids
• Naturally occurring unsaturated fatty acids contain cis double bonds.
• 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.
Oxidation of Monounsaturated Fatty Acids
During first of five remaining cycles, acyl- COA dehydrogenase step is skipped, resulting in 1 fewer FADH2
Oxidation of Polyunsaturated Fatty Acids
Results in 1 fewer FADH2 after isomerization, but 1 FADH2 is produced during the first step of the next cycle.
NADPH reduces the remaining unsaturated bond.
:star: 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 final cycle of ßoxidation of odd-numbered fatty acids.
• Bacterial metabolism in the rumen of ruminants also produces propionyl-CoA.
Oxidation of Propionyl-CoA
How "ketone bodies" are produced
:star: Ketone Bodies
• Entry of acetyl-CoA into citric acid cycle requires oxaloacetate.
• When oxaloacetate is depleted, acetyl-CoA is converted into ketone bodies.
• Three forms of ketone bodies can leave the liver: acetone, acetoacetate, and ß- hydroxybutyrate.
:star: Formation of Ketone Bodies: Generating Free CoA
A third acetyl-CoA is incorporated in the second step.
Together, two COA are freed from three acetyl- CoA.
The first step is reverse of the last step in the ß oxidation: thiolase reaction joins two acetate units.
:star: 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.
:star: The Liver Is the Source of Ketone Bodies
Ketone Bodies as Fuel
succinyl-CoA 提供 CoA
