L13: Lipids, Lipoproteins & Membranes Flashcards
What are the Structural Classes for Lipids?
- Glycerolipids
- Sphingolipids
- Sterols
What are the Functional Classes for Lipids?
- Storage
- Membrane components
- Signaling Molecules
What is Fatty Acid breakdown known as?
- Fatty acid oxidation
- Beta oxidation
- Lipid catabolism
Where does beta oxidation occur?
In the cytoplasm
What are the other names for triacylglycerols?
Neutral fats or Triglycerides
What is the structure of Triacylglycerols?
Three FA ester-linked to a glycerol backbone
What do Triacylglycerols store?
Lipids
When is C2 of glycerol a pro-chiral center?
Chiral if substituents at C1 and C3 are not identical
How are the glycerol and fatty acid chains in a triacylglycerol separated?
Hydrolysis
Under what physiological conditions are fats broken down for energy?
Starvation
When glucose levels are low in cells
Entry of Glycerol Into Glycolysis
What is the reactants?
What is the product?
Reactant: Glycerol
Product: D-Glyceraldehyde
Catabolism of Fatty Acids - Activation
What must first occur in order for fatty acids to be oxidized?
Fatty Acids must be oxidized
Catabolism of Fatty Acids - Activation
What enzyme is involved in the activation of fatty acids?
Fatty acyl-CoA synthetase
Catabolism of Fatty Acids - Activation
What is the net reaction of fatty acid activation?
Catabolism of Fatty Acids - Activation
Where does the CoA that is used in the fatty acid activation process come from?
CoA is free and in our cytosols
Catabolism of Fatty Acids - Activation
What is the reactant?
What is the product?
Reactant
- Fatty Acid
Product
- Fatty acyl-CoA
Catabolism of Fatty Acids - Transportation
What must occur in order for beta oxidation to take place in the mitochondria?
We need to move fatty acids (specifically activated fatty acyl-CoA) into the mitoschondria
Catabolism of Fatty Acids - Transportation
What is the goal of Transporting Fatty Acids?
Need to move FAs from cytosol to the mitochondrial matrix
Catabolism of Fatty Acids - Transportation
How are FAs moved from the cytosol to the mitochondrial matrix?
By using carnitine as an intermediate carrier
Catabolism of Fatty Acids - Transportation
What is the rate-limiting step in oxidation?
What is this step inhibited by?
The formation acyl carnitine is the rate-limiting step in oxidation
Inhibited by malonyl CoA
Catabolism of Fatty Acids - Transportation
What enzymes/transporters are involved in the transportation of Fatty Acids?
Where are these enzymes active?
What are these enzymes inhibited by?
- Carnitine acyltransferase I (cytosol)
- Carnitine acyltransferase II (mitochondria)
- Inhibited by malonyl CoA
Catabolism of Fatty Acids - Transportation
What are fatty acids transported into the mitochondria as?
As acylcarnitine
Catabolism of Fatty Acids
What are the 3 steps in Fatty acid catabolism - post activation and transportation?
What are the products of each step?
1) Beta oxidation of acyl chain -> acetyl-CoA
2) Oxidation of acetyl-CoA -> CO2
3) Electron transfer -> ATP
Catabolism of Fatty Acids - B oxidation
What is the goal of beta oxidation?
Introduce oxygen @ the beta carbon
Catabolism of Fatty Acids - B oxidation
Describe what occurs during beta oxidation
1) Clipping the big fatty acid molecule into small components
2) Releases acetyl CoA
3) Releases NRG in the form of reducing equivalents that produce NADH & FADH2
Comparative Energy Yield
How many carbons does glucose have?
How many carbons does palmitoyl-CoA have?
How much ATP does the complete oxidation of glucose yield?
How much ATP does the complete oxidation of palmitoyl-CoA yield?
6 Carbons
Glucose: 30-32 ATP
- apx 5 ATP/Carbon
16 Carbons
Palmitoyl-CoA: 106 ATP
- apx 6 ATP/Carbon
Comparative Energy Yield
Why is glucose still our primary energy source?
Stored as hydrophilic glycogen
- In most cells can be rapidly utilized
Fats are hydrophobic and stored in separate, specialized cells
- Takes much more time to transport and use as energy source
Energy Yield
What is the net reaction of the oxidation of Palmitoyl-CoA?
Energy Yield
What is the net reaction of the Acetyl-CoA produced in the oxidation of Palmitoyl-CoA when it enters the citric acid cycle?
Energy Yield
What is the total Net reaction of the catabolism of Palmitoyl-CoA?
How much ATP does Palmitoyl-CoA produce after it has went through oxidative phosphorylation?
108 ATP - 2 ATP = 106 ATP
Unsaturated vs. Saturated Fatty Acids
What are Fats typically made of?
Fats are typically made of a long hydrocarbon chain & contains a carboxyl group
Unsaturated vs. Saturated Fatty Acids
Describe a saturated fat
Only single bonds
- Very compact
Unsaturated vs. Saturated Fatty Acids
Describe an unsaturated fat
What does it create?
What for are the bonds in?
Contains at least one double bond
- Creates kinks, preventing tight compaction
Usually cis double bonds
- Trans double bonds lead to formation of trans fats
Unsaturated vs. Saturated Fatty Acids
Are Saturated or unsaturated fats easier to melt?
Unsaturated fats are easier to melt
Unsaturated vs. Saturated Fatty Acids
What are the 3 issues that occur in beta oxidation with unsaturated bonds?
1) Mono-unsaturated Fatty Acid with one cis double bond
2) Polysaturated FA’s
3) Odd-numbered Fatty Acids
Unsaturated vs. Saturated Fatty Acids
What is issue with probelm 1?
Need to convert into format that resembles a step in beta-oxidation
Unsaturated vs. Saturated Fatty Acids
What is the solution to problem 1?
Use an isomerase to convert cis-bind into a trans-bond
- Regular beta-oxidation util you hit double bond
- Isomerase acts
- Continued beta-oxidation
Unsaturated vs. Saturated Fatty Acids
What is the issue with problem 2?
Polyunsaturated fatty acids have multiple double bonds
Unsaturated vs. Saturated Fatty Acids
What is the solution to problem 2?
Reduce a double bond to a single bond
- Reductase enzyme reduces to one double bond
- Isomerase moved double bond to produce beta-oxidation intermediate (double bond between alpha and beta)
Unsaturated vs. Saturated Fatty Acids
What is the issue with problem 3?
Last round of beta oxidation produced propionyl-CoA (3C molecule)
Unsaturated vs. Saturated Fatty Acids
What is the solution to problem 3?
Turn it unto succinyl-CoA (a 4C TCA intermediate)
- Carboxylate propionyl-CoA using propionyl-CoA carboxylase
- Carboxylation uses ATP and biotin - Convert D-methulmalonyl-CoA to L using methylmalonyl-CoA mutase
- The carbonyl/S-CoA and H-atom “swap places”
Ketone Bodies and Ketogenesis
Once FAs are catabolized into Acetyl-CoAs
What pathways could they enter?
TCA Cycle or Ketogenesis
Ketone Bodies and Ketogenesis
Describe Ketone Bodies
- Derivation?
- Purpose?
- When is it made?
- Number of main molecules
1) Derived from acetyl-CoA
2) Important fuels transported throughout the body (hydrophilic)
3) Made during starvation
4) 3 Main molecules
Ketone Bodies and Ketogenesis
What are the Main 3 Ketone bodies?
Acetone
Acetoacetate
beta-Hydroxybutyrate
Ketone Bodies and Ketogenesis
What is Ketogenesis?
Where does it take place, what does it use?
When does it take place?
- Generates Ketone bodies
- Occurs in the liver using acetyl CoA
- Takes place during starvation
Ketone Bodies and Ketogenesis
What occurs during starvation?
- Gluconeogenesis depletes TCA intermediates
- TCA slows and acetyl CoA builds
- acetyl-CoA -> acetoacetate
- KBs are sent to the brain, muscle, heart, and kidneys
Ketone Bodies and Ketogenesis
What is the net reaction of Ketogenesis?
What is the enzyme associated with the 4 condensation steps of ketogenesis?
Ketone Bodies and Ketogenesis
What property makes ketone bodies be able to be transported in the bloodstream from producing organs to the consumer organs that use ketone bodies as fuel?
Ketone bodies contain oxygen in higher proportions so they are soluble and can be transported in the bloodstream from producing organs to the consumer organs that use ketone bodies as fuel
Ketone Bodies and Ketogenesis
How Does Acetyl-CoA interact with membranes?
What determines this interaction?
Acetyl-CoA does not cross membranes because of CoA
Beta Oxidation vs. Biosynthesis
Carbon Units
Beta: C2
Bio: C2
Beta Oxidation vs. Biosynthesis
C2 Product/Donor
Beta: Acetyl-CoA
Bio: Malonyl-CoA
Beta Oxidation vs. Biosynthesis
Electron Acceptor/Donor
Beta: NAD+/FAD
Bio: NADPH
Beta Oxidation vs. Biosynthesis
Location
Beta: Mitochondria
Bio: Cytosol
FA Biosynthesis
Describe Acetyl-CoA in the context of FA Biosynthesis
How does Acetyl-CoA enter cytosol?
Is it exported directly?
- Acetyl-CoA must be transported from the mitochondria into the cytosol (where biosynthesis occurs)
- Acetyl-CoA cannot be exported directly
FA Biosynthesis
How is Acetyl-CoA exported into the cytosol?
How much ATP does the exportation process cost?
What bi-product does this process produce?
- Lysed to Acetyl-CoA (C2)
- The remains (C3 or C4) are re-imported
- 2 ATP per acetyl-CoA
- Generates cytosolic NADPH
FA Biosynthesis
What is the goal of the Acetyl Group Shuttle?
Transport an acetyl CoA equivalent from the matrix to the cytosol
Precursor for FA Biosynthesis
What are the 6 steps in transporting Acetyl-CoA into the cytosol?
FA Biosynthesis
What are FAs synthesized from?
What is the energy source for this synthesization?
- FAs are synthesized form Malonyl-CoA, not directly from acetyl-CoA
- Acetyl-CoA carboxylase forms malonyl-CoA using ATP
FA Biosynthesis
What is the commitment step in FA synthesis?
Formation of malonyl-CoA
FA Biosynthesis
What is the formation of malonyl-CoA inhibited by?
Glucagon, epinephrine, palmitoyl-CoA
FA Biosynthesis
What is the formation of malonyl-CoA activated by?
Citrate
FA Biosynthesis
What is the precursor step to FA Synthesis?
What is the 4-Step Sequence of FA Synthesis?
What enzyme is involved in FA synthesis?
What happens after the 4 step sequence of FA synthesis?
Precursor: Fatty Acid Synthase is loaded with acetyl-CoA and the ACP subunit with malonyl-CoA
4 Steps of Synthesis
1) Condensation
2) Reduction using NADPH
3) Dehydration
4) Reduction using NADPH
FA Synthase is involved in FA synthesis
- Very complex, has 7 subunits
Post Synthesis
1) Growing chain moves to KS
2) ACP is reloaded with malonyl-CoA for the 2nd round
After 7 cycles , a palmitate-specific thioesterase cleaves the completed fatty acid from FA synthase
FA Biosynthesis
What is the NET reaction of the biosynthesis of palmitate?
FA Biosynthesis
How are fatty acid synthesis and breakdown regulated and coordinated?
How does this coordination occur?
The opposing process must be coordinated so only one occurs at a time
- Coordination occurs through malonyl CoA
as it initiates FA synthesis and inhibits beta oxidation
TAG and Glycerophospholipids Synth
What is the precursor for both?
Phosphatic acid
- Made from L-G3P
- 2 FAs attached with phosphate group
TAG and Glycerophospholipids Synth
What are the 2 steps in Triacyl-Glycerol Synth?
1) Replace phosphate group with OH
2) Replace OH group with FA
TAG and Glycerophospholipids Synth
What are the 2 methods for steps in Glycerophospholipids Synth?
Method 1: Activation of phosphatic acid
Method 2: Activation of the head group
