GProteinCoupled Receptors and Second Messengers

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G-Protein-Coupled Receptors and Second Messengers

• S 2006 BIOC 3406
• 1-19-2006

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Elements of G-Protein signalling

• A membrane bound receptor with seven
  transmembrane helices
• An membrane bound enzyme that generates an
  intracellular second messenger
• A G-protein (guanosine nucleotide-binding
  protein)

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The human genome encodes more than 1000 members
of this family of receptors, specialized for
transducing messages as diverse as light, smells,
tastes, and hormones. Nelson and Cox, Lehninger
Principles of Biochemistry, p 435
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The ß-adrenergic receptor

• Prototype of G-protein system
• Agonists
• Compounds that bind the receptor and cause the
  same effects as the natural ligand
• Antagonists
• Compounds that bind without causing a response,
  thus blocking the action
• ß-adrenergic receptors of muscle, liver, adipose
  tissue mediate changes in fuel metabolism.

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ß-adrenergic receptor

• Seven 20-28 non-polar residue sections
• Also called
• Serpentine receptors
• G Protein-coupled receptors (GPCR)
• 7 transmembrane segment (7tm) receptors

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Phosphodiesterase inhibited by caffeine,
theophylline
Cyclic nucleotide phosphodiesterase
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Bioenergetics and Metabolism

• S 2006 BIOC 3406
• 1-19-2006

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Complexity of metabolism

• Hundreds of enzyme-catalyzed reactions
• Hundreds of compounds

Simplicity of metabolism

• Central pathways small subset
• Small number of important compounds

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Energy and Materials

• C, N, and O are recycled
• Energy is degraded to heat

Intermediary Metabolism

• All the chemical activities that produce and
  degrade low molecular weight (lt1000) compounds

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Catabolism v. Anabolism

• Two sets of enzymes (some steps common)
• Avoids futile cycling
• Allows regulation by controlling the distinct
  enzyme systems.
• Paired steps tend to be in different
  compartments
• cytosol v. organelle

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Regulation

• Concentration of substrate
• Allosteric regulation
• e.g., feedback inhibition
• external signals (hormones, etc.)

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General Reaction Categories(overlapping)

• Oxidation-reduction
• Carbon-carbon bond formation or scission
• Rearrangements
• Group transfers
• Free radical reactions

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Dehydrogenases -- H2 Oxidases -- C-O
bond Oxygenases -- CO bond with O2
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electrophilic carbonyl carbon
stabilization by resonance
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Phosphorus in PO43- is electrophilic