Fatty Acid Oxidation (Catabolism) Flashcards
Lipid Metabolism: Chapter 20
ß-Oxidation Hypothesis
ß-Oxidation Hypothesis
- breakdown occurs at the C that is ß to the carboxyl group
-
fatty acid is progressively degraded by two carbon units
- Aka. breaking down 2 C’s at a time
- confirmed in the 1950’s
Why is the degradation of fatty acids called ß Oxidation?
Why is the degradation of fatty acids called ß Oxidation?
The degradation of fatty acids is called ß Oxidation b/c breakdown occurs at the C that is ß to the carboxyl group
Fatty Acid Activation
Fatty Acid Activation
Before the fatty acids can be oxidized, they must be activated with CoA. The reaction is catalyzed by Acyl-CoA synthetases:
Fatty Acid + CoA + ATP ⇔ fatty acyl-CoA + AMP + PPi
- the reaction is catalyzed by acyl-CoA synthetases*
- this is a two step mechanism*
Acyl-CoA Synthases
Acyl-CoA Synthases:
- Catalyze the ATP-dependent transfer of a thiol group (CoA)
- At least 3 different enzymes that differ in their chain-length specificity
Mechanism of Fatty Acid Activation
Describe the activation of fatty acids with CoA
Describe the activation of fatty acids with CoA
Before the fatty acids can be oxidized, they must be activated with CoA. The reaction is catalyzed by Acyl-CoA synthetases:
Fatty Acid + CoA + ATP ⇔ fatty acyl-CoA + AMP + PPi
- catalyzed by acyl-CoA synthetases
- which catalyze the ATP-dependent transfer of a thiol group (CoA)
- ATP activates the fatty acid for reaction with thiol
- pyrophosphate hydrolysis drives the reaction
- Activation occurs in the cytosol
Fatty Acid Transport into the Mitochondrial Matrix
Fatty Acid Transport into the Mitochondrial Matrix
- fatty acid oxidation occurs inside the mitochondrial matrix
- fatty acids are transferred to carnitine
Carnitine
Carnitine
-
Carnitine carries acyl groups across mitochondrial membrane
- the fatty acids are converted back to acyl-CoAs in the mitochondrion
- Carnitine is returned to the cytosol
ß Oxidation of Fatty Acids to Acetyl-CoA
ß Oxidation of Fatty Acids to Acetyl-CoA
Four recurring reactions
- oxidation
- hydration
- oxidation
- thiolysis
Each recurrence:
- shortens the chain by 2 C’s
- produces Acetyl-CoA
- which can make 1 GTP, 1 FADH2, & 3 NADH in the CAC
- produces two reducing equivalents
- FADH2 for the ET chain
- NADH + H+
3 Names for the Citric Acid Cycle (CAC)
3 Names for the Citric Acid Cycle (CAC)
- Krebs Cycle
- Citric Acid Cycle (CAC)
- Tricarboxylic Acid Cycle (TCA cycle)
Overview of Catabolism (Stages)
Overview of Catabolism (Stages)
Stage 1: Energy stores are broken down into their building blocks
Stage 2: Building blocks are degraded to the common intermediate acetyl CoA
Stage 3: Energy Production Payoff
- In the CAC, acetyl groups are oxidized to CO2, generating lots of e- in the form of NADH and FADH2
- The e- are converted to ATP via the Electron Transport Chain (ETC) & oxidative phosphorylation
Where does Fatty Acid Activation occur?
Where does Fatty Acid Activation occur?
the cytosol
Where does ß Oxidation occur?
Where does ß Oxidation occur?
the mitochondria
Where does Fatty Acid Oxidation occur?
Where does Fatty Acid Oxidation occur?
the mitochondrial matrix
Yield of products per round of ß Oxidation
Yield of products per round of ß Oxidation
Fatty acid oxidation is highly exergonic
Yield Per Round :
of the 4 recurring reactions
Direct
w/Krebs Cycle
1 Acetyl-CoA
1 GTP (=ATP)
1 FADH2
3 NADH
1 FADH2
1 FADH2
1 NADH
1 NADH
How many ATP’s is FADH2 equivalent to? NADH?
How many ATP’s is FADH2 equivalent to? NADH?
1 FADH2 = 1.5 ATP
1 NADH = 2.5 ATP
Oxidation of Unsaturated Fatty Acids requires _____________________________________
to create typical 𝛽 oxidation intermediates.
Oxidation of unsaturated fatty acids requires double bond isomerization & reduction to create typical 𝛽 oxidation intermediates
The final round of 𝛽 oxidation of odd-chain fatty acids produces _______________ and _____________.
The final round of 𝛽 oxidation of odd-chain fatty acids produces 1 propionyl-CoA and acetyl-CoA
What is the fate of propionyl-CoA and acetyl-CoA?
The fate of propionyl-CoA and acetyl-CoA:
final round of ß oxidation gives propionyl-CoA and acetyl-CoA rather than two molecules of acetyl-CoA.
Propionyl-CoA is oxidized to succinyl-CoA for entry into the CAC
What reaction is catalyzed by methylmalonyl-CoA mutase ?
This reaction is involved in the pathway to convert propionyl-CoA to succinyl-CoA, which will ultimately be converted to acetyl-CoA for use in the Citric Acid Cycle
What are the important metabolic function of ketone bodies?
Important metabolic function of ketone bodies
Ketone bodies are important metabolic fuels for peripheral tissues:
- Heart
- Skeletal muscle
- Brain during starvation
5 Differences between fatty acid ß oxidation and fatty acid biosynthesis
5 differences btwn Fatty Acid ß Oxidation & Biosynthesis
- Cellular location - synthesis takes place in the cytoplasm; degradation takes place in the mitochondrial matrix
- Acyl group carrier - intermediates in fatty acid synthesis are covalently linked to the sulfhydryl group of acyl carrier protein (ACP); breakdown intermediates are covalently linked to the sulfhydryl group of CoA
- Electron acceptor/donor - the reductant in fatty acid synthesis is NADPH; whereas the oxidants in fatty acid degradation are NAD+ and FAD
- Stereochemistry of the hydration/dehydration rxn
- The form in which C2 units are produced/donated - the growing chain is elongated by C2 units from malonyl-CoA (a C3 compound); Acetyl-CoA is the C2 product from oxidation
What does the tricarboxylate transport system do?
The tricarboxylate transport system transfers acetyl-CoA into the cytosol for fatty acid synthesis
What enzyme is involved in the formation of malonyl-CoA ?
Acetyl CoA-carboxylase (ACC) is the enzyme involved in the formation of malonyl-CoA
