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

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