This class
Organization of cellular energy metabolism:
entry of carbon fuelstransport within cellmetabolic interconversions in cytosoltransport and oxidation in
mitochondriaoxidative phosphorylation
Energy Metabolism
Which type(s) of cells produce
energy?
Energy Metabolism
Why do we need constant input of
energy?
Energy Metabolism
3 major metabolic fuel types:
Carbohydrate (glucose)Protein (amino acids)
Lipids (fatty acids)
1. Entry of carbon fuels: plasma membrane transport
glucoseaminoacids
fattyacids
glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
GLUT4 in isolated adipocytes
1. Entry of carbon fuels: plasma membrane transport
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
glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
glucoseaminoacids
fattyacids
GLUT
1. Entry of carbon fuels: plasma membrane transport
glucoseaminoacids
fattyacids
GLUT
?
1. Entry of carbon fuels: plasma membrane transport
Fatty acid transport – plasma membrane
Fatty acid transport via an ATP-driven pump?
1. Entry of carbon fuels: plasma membrane transport
• Glucose – specific transporters (GLUT)
• Amino acids – diffusion and/or transporters (many!)
• Fatty acids – still unknown!
2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose
2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose aminoacids
2. Transport within the cell
glucoseaminoacids
fattyacids
GLUT
Glucose-6P
glucose aminoacids
Fatty acid binding protein
(FABP)
2. Transport within the cell
• Glucose – soluble; trapped by conversion to G-6P
• Amino acids – diffusion/transport
• Fatty acids - FABP
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
1 glucose
↓
2 pyruvates
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
2x pyruvate
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
(2x) pyruvate
mitochondria
lactate
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
Transaminationdeamination
Oxidation of carbon
skeleton
GLUT
Glucose-6P
glucose aminoacids
Fatty acids
3. Metabolic interconversions in the cytosol
Fatty acyl-CoA
Acyl-CoA synthetas
e
3. Metabolic interconversions in the cytosol
• Glucose: → pyruvate → lactate
• Amino acids → trans/deamination → oxidation
• Fatty acids: → fatty acyl-CoA
4. Import into mitochondria & catabolism
Pyruvate transport & catabolism
Import of fatty acids into mitochondria
Catabolism in the mitochondrial matrix
Catabolism in the mitochondrial matrix
4. Import into mitochondria & catabolism
pyruvate → PyrC → PDH → TCA
amino acids: many
fatty acids → CPT → β-ox → TCA
Organization and compartmentalization of fuel
catabolism - summary
The mitochondrion – energy transduction central
How does it work?
http://www.sci.sdsu.edu/TFrey/MitoMovie.htm
The (in)efficiency of oxidative phosphorylation
Proton leak: Non-ohmic (v. high leak at high membrane potential)
Purpose of proton leak?Why isn’t ox-phos more efficient?
Purpose of proton leak?
Heat production?
Purpose of proton leak?
Heat production? (only in some cases)
Functions of UCPs
UCP1 - Only in mammals- Only in brown adipose tissue– heat production
Functions of UCPs
Other UCPs- Ubiquitous (nearly; including ectotherms)– prevent membrane potential getting to high?
Purpose of proton leak?
Heat production? (only in some cases)
Reduce production of reactive oxygen?
Rapid rest to work transitions (idling speed)?
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
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
Next week:
Finish reading chapter 3Read posted review