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This class
Organization of cellular energy metabolism:
entry of carbon fuelstransport within cellmetabolic interconversions in cytosoltransport and oxidation in
mitochondriaoxidative phosphorylation
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Energy Metabolism
Which type(s) of cells produce
energy?
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Energy Metabolism
Why do we need constant input of
energy?
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Energy Metabolism
3 major metabolic fuel types:
Carbohydrate (glucose)Protein (amino acids)
Lipids (fatty acids)
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1. Entry of carbon fuels: plasma membrane transport
glucoseaminoacids
fattyacids
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glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
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GLUT4 in isolated adipocytes
1. Entry of carbon fuels: plasma membrane transport
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GLUT protein isoforms
Same basic structure
13 members (isoforms) now recognized
Differ in tissue specificity, kinetic properties (including sensitivity to insulin)
1. Entry of carbon fuels: plasma membrane transport
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glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
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glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
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glucoseaminoacids
fattyacids
GLUT
?
1. Entry of carbon fuels: plasma membrane transport
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Fatty acid transport – plasma membrane
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Fatty acid transport via an ATP-driven pump?
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1. Entry of carbon fuels: plasma membrane transport
• Glucose – specific transporters (GLUT)
• Amino acids – diffusion and/or transporters (many!)
• Fatty acids – still unknown!
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2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
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2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose
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2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose aminoacids
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2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose aminoacids
Fatty acid binding protein
(FABP)
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2. Transport within the cell
• Glucose – soluble; trapped by conversion to G-6P
• Amino acids – diffusion/transport
• Fatty acids - FABP
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
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1 glucose
↓
2 pyruvates
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
2x pyruvate
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
(2x) pyruvate
mitochondria
lactate
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
Transaminationdeamination
Oxidation of carbon
skeleton
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GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
Fatty acyl-CoA
Acyl-CoA synthetas
e
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3. Metabolic interconversions in the cytosol
• Glucose: → pyruvate → lactate
• Amino acids → trans/deamination → oxidation
• Fatty acids: → fatty acyl-CoA
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4. Import into mitochondria & catabolism
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Pyruvate transport & catabolism
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Import of fatty acids into mitochondria
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Catabolism in the mitochondrial matrix
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Catabolism in the mitochondrial matrix
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4. Import into mitochondria & catabolism
pyruvate → PyrC → PDH → TCA
amino acids: many
fatty acids → CPT → β-ox → TCA
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Organization and compartmentalization of fuel
catabolism - summary
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The mitochondrion – energy transduction central
How does it work?
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The (in)efficiency of oxidative phosphorylation
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Proton leak: Non-ohmic (v. high leak at high membrane potential)
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Purpose of proton leak?Why isn’t ox-phos more efficient?
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Purpose of proton leak?
Heat production?
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Purpose of proton leak?
Heat production? (only in some cases)
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Functions of UCPs
UCP1 - Only in mammals- Only in brown adipose tissue– heat production
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Functions of UCPs
Other UCPs- Ubiquitous (nearly; including ectotherms)– prevent membrane potential getting to high?
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Purpose of proton leak?
Heat production? (only in some cases)
Reduce production of reactive oxygen?
Rapid rest to work transitions (idling speed)?
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Inefficiency of oxidative phosphorylation
Proton leak
Present in mitochondria from all organisms (including ectotherms)
Substantial (~20% of cellular MR)
Basal rate of leak increased by protein catalysts (UCPs) in some cell types
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Metabolic organization of animal cells
• Regulated membrane transport of energy substrates
• Protein-mediated intracellular transport of some energy substrates
• Mitochondrial membrane transporters
• TCA cycle as a central node in catabolic pathways
• Proton motive force and ATP synthesis
• Inefficiency of ox-phos
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Next week:
Finish reading chapter 3Read posted review