Lecture 20: Fat Metabolism Flashcards
1
Q
Triacylglycerol
A
- Extra carbons are stored in triacylglycerol molecules, primarily in fat cells but also in muscle and other tissues
- Acyl chains are connected to a glycerol backbone via ester bonds
- Fatty acyl chains are saturated for close packing
- Chains must be hydrolyzed off for use
2
Q
Beta-andergenic receptor
A
- Epinephrine and glucagon signal via GPCRs to activate lipases
- Lipases hydrolyze ester bonds to produce free fatty acids(FFAs) and glycerol
- FFAs are transported in blood glucose via albumin for cellular use
3
Q
Fat Mobilization via GPCR signaling
A
- Epinephrine and glucagon bind to GPCRs on adipose cells
- Signaling response involves the release of Ga-GTP, activation of adenyl cyclase and cAMP production, leading to PKA activation
- PKA phosphorylates and activates triacylglycerol lipase(also known as hormone sensitive lipase)
- TAGs are hydrolyzed to 3 fatty acids(+ glycerol) that are released in blood and transported via albumin
4
Q
Fatty Acid Activation in the Cytoplasm
A
- Acyl chains are trapped in the cell by covalent addition of coenzyme A
- Acyl CoA Synthetase catalyzes a reversible reaction uses ATP(-> AMP) to form fatty acyl CoA
- Pyrophosphate(PPi) hydrolysis to 2 Pi is favorable and drives the reaction in forward direction
5
Q
ATP -> AMP is energetically inefficient
A
- 95% of the ATP is made in oxidative phosphorylation using ADP as a substrate
- In order for ATP to be made from AMP, AMP must be converted to ADP by sacrificing a 2nd ATP
- Fatty acid activation of CoA requires 2 ATP(1 for activation and 1 for ADP production) and 1 H2O to hydrolyze PPi
6
Q
Acyl CoA and Beta oxidation
A
- Acyl CoA is made in the cytoplasm, but beta-oxidation occurs inside mitochondrial matrix
- Acyl CoA can pass through outer membrane into intermembrane space via porins, but cannot cross the inner membrane since there is no transport mechanism
- CoA is too large and water soluble making it unable to cross membranes
7
Q
Carnitine Shuttle
A
- The carnitine shuttle regulates what comes into the mitochondria
- Carnitine Acyltransferase 1(CAT 1) moves the acyl chain onto carnitine from CoA
- Acyl carnitine is translocated across the innter membrane in exchange for carnitine
- Carnitine Acyltransferase 2(CAT 2) moves acyl back onto CoA
- Acyl CoA can then be used in beta-oxidation
8
Q
How many rounds of beta oxidation are needed to breakdown 16:0 CoA
A
- rounds = (n/2) - 1
- 16:0 CoA is 16 carbons, Acetyl CoA is 2 carbons
- Breakdown repeats, last round starts with 4:0 and produces 2 Acetyl CoAs
9
Q
4 Steps of Beta Oxidation
A
- Fatty acid oxidation occurs at the beta-carbon(number 3 carbon in fatty acid chain)
- Acyl CoA dehydrogenase: produces FADH2 and creates a double bond in the fatty acid chain
- Hydratase: adds water across the double bond(beta-OH)
- Dehydrogenase: produces NADH and creates a keto group on the beta carbon in the chain
- Thiolase: uses CoA to release acetyl-CoA, producing a fatty acyl CoA chain with 2 fewer carbons
10
Q
Summary-Fatty Acid Breakdown
A
- Epinephrine and glucagon required for TAG breakdown
- Fatty acids travel in blood stream bound to albumin and enter the tissues
- Fatty acids are activated in the cytoplasm by acyl CoA synthetase, requiring 2 ATP
- The carnitine shuttle controls fatty acid entry into matrix(CAT 1, translocate, CAT 2) in exchange for free carnitine
- Acyl chains are broken down in beta-oxidation producing Acetyl CoA, NADH, and FADH2
- Beta oxidation can produce a huge amount of ATP using citric acid cycle and oxidative phosphorylation
11
Q
Using Fats as Fuel
A
- In order to generate ATP in mitochondria, Acetyl-CoA from fat degradation needs to be processed via citric acid cycle
- CAC is dependent on amount of oxaloacetate present
- In order to efficiently make ATP from fat, cells need oxaloacetate
- Oxaloacetase can be made from amino acids or pyruvate by pyruvate carboxylase
- Need a blend of fuels, both glucose, amino acids and fats, for efficient energy production
12
Q
Hormonal Response and Fat Synthesis
A
- As glucose levels rise, insulin signals for glucose uptake and catabolism in glycolysis. Fats and amino acids will be imported for use in the cell
- As ATP levels rise, glycolysis slows down and excess glucose is stored as glycogen in muscle and liver cells
- As ATP and NADH levels rise in the mitochondria, the citric acid cycle slows down, allowing for synthesis of fat from Acetyl-CoA
- Excess macromolecules will be first broken down to smaller precursors and energy that can be used to make fats, but Acetyl CoA is made in mitochondria
13
Q
Steps in Fatty Acid Synthesis
A
Fatty Acid Processing Steps:
- 1. Export of mitochondrial Acetyl CoA to the cytoplasm for fat synthesis
- 2. Carboxylation of acetylene CoA to malonyl CoA by Acetylene CoA Carboxylase(ACC)
- 3. Use of malonyl CoA to form 16:0 fatty acid chains
14
Q
Acetyl CoA is exported as citrate
A
- Coenzyme A cannot cross inner mitochondrial membrane
- Citrate synthase makes citrate in TCA cycle, which can cross inner membrane
- Citrate broken down by different enzymes to recreate acetyl-CoA, regenerating pyruvate
- Pyruvate can return to mitochondria while Acetyl CoA is used for synthesis of fatty acyl chains in cytoplasm
15
Q
Fatty Acid Synthesis is a Anabolic Process
A
- Acyl chain synthesis occurs in the cytoplasm
- 2 enzymes are needed: Acetyl CoA Carboxylase and Fatty Acid Synthase
- Acetyl CoA carnoxylase converts Acetyl CoA to malonyl CoA, an activated 2 carbon carrying precursor for fatty acid synthesis
- Acetyl CoA Carboxylase is the committed and regulated step for fatty acid synthesis
- Acetyl CoA Carboxylase uses ATP, while Fatty Acid Synthase uses NADPH as reducing power
