This class
Organization of cellular energy metabolism:
entry of carbon fuels
transport within cell
metabolic interconversions in cytosol
transport and oxidation in mitochondria
oxidative 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
glucose
amino
acids
fatty
acids
1. Entry of carbon fuels: plasma membrane transport
glucose
GLUT
amino
acids
fatty
acids
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
glucose
GLUT
amino
acids
fatty
acids
1. Entry of carbon fuels: plasma membrane transport
glucose
GLUT
amino
acids
fatty
acids
1. Entry of carbon fuels: plasma membrane transport
glucose
amino
acids
fatty
acids
GLUT
?
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
glucose
GLUT
amino
acids
fatty
acids
2. Transport within the cell
glucose
GLUT
glucose
Glucose-6P
amino
acids
fatty
acids
2. Transport within the cell
glucose
amino
acids
GLUT
glucose
Glucose-6P
amino
acids
fatty
acids
2. Transport within the cell
glucose
amino
acids
fatty
acids
GLUT
glucose
Glucose-6P
amino
acids
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
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
amino
acids
Fatty
acids
1 glucose
↓
2 pyruvates
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
2x pyruvate
amino
acids
Fatty
acids
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
(2x) pyruvate
mitochondria
amino
acids
lactate
Fatty
acids
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
amino
acids
Fatty
acids
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
amino
acids
Transamination
deamination
Oxidation of
carbon skeleton
Fatty
acids
3. Metabolic interconversions in the cytosol
GLUT
glucose
Glucose-6P
Fatty
acids
amino
acids
Acyl-CoA
synthetase
Fatty acyl-CoA
3. Metabolic interconversions in the cytosol
•
Glucose:
•
Amino acids
•
Fatty acids:
→
pyruvate
→ trans/deamination
→
fatty acyl-CoA
→
lactate
→
oxidation
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:
potential)
Non-ohmic (v. high leak at
high membrane
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 3
Read posted review