Transcript Fatty Acid Catabolism

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
A) 1, 7, 2, 2
B) 6, 3, 4, 2
C) 1, 2, 3, 4
D) 2, 5, 2, 4
5. hydration
6. phosphorylation
7. rearrangement
3. The conversion of the laurate CoA (a 12-carbon acylCoA) to carbon dioxide via βoxidation, 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
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
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
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
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
Step 2: Enoyl CoA Hydratase
• Similar to fumarate
hydratase from citric acid
cycle
• Addition of water
• No energy
cost/production
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
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
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
Alternate Fate of Acetyl CoA
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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
Regulation
Answers
1.
2.
3.
4.
5.
A
D
B
D
D