Nucleotides Critical For Biological Signal Transduction

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Nucleotides Critical ForBiological Signal
Transduction
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Signal Transduction
Signal molecules are often extracellular
Receptor is often embedded in the cellular
membrane
The intracellular signal is often propagated with
the help of a nucleotide
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Nucleotides that propagate signal transduction in
mammalian cells
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cAMP-mediated signaling
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Catalysis by adenylyl cyclase
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The cAMP signal is terminated by the enzyme
cyclic nucleotide phosphodieterase
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The action of many hormones is mediated by cAMP
signaling
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Mammalian guanylyl cyclases
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Catalysis by the enzyme Guanylyl cyclase
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ANF receptor-type guanylyl cyclases

• Atrial natriuretic factor (ANF) is a hormone
  released by heart cells in the atrium when
  increased blood volume stretches the heart.
• ANF is carried in the blood and acts on guanylyl
  cyclase of kidney cells.
• The rise in cGMP in kidney cells causes excretion
  of Na and H2O.
• H2O loss decreases blood volume and counters the
  stimulus that caused ANF release by the heart
  cells.

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Guanylin receptor-type guanylyl cyclases

• Guanylin is an intestinal peptide that regulates
  Cl- secretion in the intestine.
• Guanylin binding to the extracellular side of the
  receptor causes synthesis of cGMP in intestinal
  epithelial cells, causing secretion of Cl- and
  H2O into the intestine.
• An endotoxin produced by some bacteria also binds
  to the receptor, decreasing absorption of H2O by
  the intestinal epithelial cells and causing
  diarrhea.

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Soluble Guanylyl cyclases

• Soluble guanylyl cyclases lack a membrane anchor
  region and are soluble in the cytoplasm of a
  cell.
• In heart cells cGMP production brings about less
  forceful contractions by expelling Ca2 from the
  heart muscle cells

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Soluble guanylyl cyclase is activated by nitric
oxide (NO)
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Nitroglycerin and Angina

• Individuals with heart disease often experience
  chest pain (angina).
• To alleviate the pain and prevent a heart attack,
  nitroglycerin tablets are ingested.
  Nitroglycerin is metabolized, producing nitric
  oxide (NO).
• The NO binds to the heme of the soluble guanylyl
  cyclase, producing cGMP, activating calcium pumps
  that expel Ca2 from heart muscle cells,
  decreasing the force of heart muscle contractions.

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cGMP and Vision
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Exam 1

• Thursday February 8
• 5 615
• Julian Hall Room 225