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

glucose amino acids fatty acids 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

glucose amino acids fatty acids GLUT 1. Entry of carbon fuels: plasma membrane transport

glucose amino acids fatty acids GLUT 1. Entry of carbon fuels: plasma membrane transport

glucose amino acids fatty acids 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 glucose amino acids fatty acids GLUT

2.Transport within the cell glucose amino acids fatty acids GLUT Glucose-6P glucose

2.Transport within the cell glucose amino acids fatty acids GLUT Glucose-6P glucose amino acids

2.Transport within the cell glucose amino acids fatty acids GLUT Glucose-6P glucose 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

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol

1 glucose ↓ 2 pyruvates

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol 2x pyruvate

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol (2x) pyruvate mitochondria lactate

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol Transamination deamination Oxidation of carbon skeleton

GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol Fatty acyl-CoA Acyl-CoA synthetase

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

4.Import into mitochondria & catabolism pyruvate → P yrC → 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?

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 3 Read posted review