Download Fatty Acid Catabolism

3/18/2013
Fatty Acid Catabolism
C483 Spring 2013
1. Which lipid form is transported across the inner mitochondrial membrane before β‐oxidation? A) Acylcarnitine. B) Fatty acyl CoA. C) Acetoacetyl CoA. D) Lysophospholipid CoA. 2. There are four steps in the β‐oxidation pathway. Some reaction types are listed below. Give the proper reaction types in the order that they occur in the β‐oxidation pathway.
1. Condensation
2. Oxidation
3. Reduction
4. Thiolysis
5. hydration
6. phosphorylation
7. rearrangement
A) 1, 7, 2, 2 B) 6, 3, 4, 2 C) 1, 2, 3, 4 D) 2, 5, 2, 4 1
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3. The conversion of the laurate CoA (a 12‐carbon acylCoA) to carbon dioxide via β‐
oxidation, the citric acid cycle and oxidative phosphorylation yield approximately ________ ATP equivalents. A) 78 B) 80 C) 82 D) 84
4. A patient is found to have a high concentration of cholesterol in the blood and deposits of cholesterol under the skin. The patient is diagnosed with familial hypercholesterolemia. What is the likely cause of this condition? A) A deficiency in insulin production by the pancreas. B) Insufficient chylomicron concentration in the blood. C) Overproduction of lysosomal lipases. D) Lack of LDL receptors on the surfaces of nonhepatic cells. 5. Ketone bodies form when ______________ is in low concentration:
A) Acetyl CoA
B) Triacylglyceride
C) Cholesterol
D) oxaloacetate
Overview
• Lipids as a fuel source—diet
• Beta oxidation – Mechanism
– ATP production
• Ketone bodies as fuel
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TAG and FA
• High energy
– More reduced
– Little water content
– 9 Cal/g vs 4 Cal/g for carbs
• Unsaturated FA
• Glycerol
Digestion
• Cross from intestine into bloodstream
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Lipoprotein Metabolism
• Liver is the packaging center
• VLDL are sent out of liver
• Constant cycling of LDL in blood
• Genetic cholesterol problem: no LDL receptors in non‐liver cells
• HDLs are “good cholesterol”
Utilization Stage 1:
Mobilization
Hormone Sensitive Lipase
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Utilization Stage 2:
Transport into Matrix
• FA  FA‐CoA costs ATP AMP (2 ATP equivalents)
• Carnitine ester: high energy bond
• Mammals also degrade FA in peroxisome
• Major site of regulation of FA degradation
Utilization Stage 3: Beta Oxidation
• Four step process
• Production of – QH2
– NADH
– Acetyl CoA
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Step 1: Acyl CoA Dehydrogenase
• Similar to succinate DH from citric acid cycle
• Prosthetic FAD/FADH2
• High energy electrons passed on to QH2
• 1.5 ATP
O
R
SCoA
O
R
SCoA
Step 2: Enoyl CoA Hydratase
• Similar to fumarate
hydratase from citric acid cycle
• Addition of water
• No energy cost/production
O
R
SCoA
OH
R
O
SCoA
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Step 3: 3‐hydroxyacyl CoA DH
• Similar to malate DH from citric acid cycle
• Oxidation of secondary alcohol to ketone
• NADH production
• 2.5 ATP
OH
O
R
SCoA
O
O
R
SCoA
Step 4: Thiolase
• CoA is used as a nucleophile in a “nucleophilic acyl substitution”
• FA shortened by 2 carbons
• Acetyl CoA produced
• 10 ATP through CAC
O
O
R
SCoA
HS-CoA
O
R
O
SCoA
SCoA
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ATP Accounting
• How much ATP is netted from palmitate (16 carbons)?
– Cost 2 ATP to activate to palmitate CoA
– Run through beta oxidation SEVEN times
• 7 QH2 = 10.5 ATP
• 7NADH = 17.5 ATP
– 8 acetyl CoA produced = 80 ATP
• Total: 106 ATP, or 6.625 ATP per carbon
• Compare to glucose, which is 5.33 ATP per C
Processing Other FA
• Unsaturated and trans fatty acids
– Enzymes can handle processing
– Produce 1.5 ATP less per unsaturation (why?)
• Odd chain fatty acids
– Rare, but do occur in diet
– One of 2 requirements for Vitamin B12 (cobalamine) in human diet
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Alternate Fate of Acetyl CoA
•
•
•
•
•
•
Fasting, Diabetes
Glycolysis is down, gluconeogenesis is up
Oxaloacetate depleted
Citric acid cycle has diminished capacity
Acetyl CoA levels build up
Ketone bodies are formed
Ketone Bodies
• Water soluble form of lipids
• Less potential energy than FA
• Main energy source of brain in starvation
• Also used in muscle and intestine
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Regulation
Answers
1.
2.
3.
4.
5.
A
D
B
D
D
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