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second messenger

BiochemistryCell signalingG protein-coupled receptorsHormones

Summary

A second messenger is a small intracellular molecule or ion (cAMP, IP₃, DAG, Ca²⁺) released after an extracellular first messenger binds a surface receptor; it relays and amplifies the signal. Testable: hydrophilic hormones usually signal this way, and blocking its synthesis or breakdown shifts the response.

Detail

Meaning: This is a cell-signaling idea, tested in biochemistry and biology rather than in organic chemistry. The first messenger is the ligand outside the cell. It binds a receptor, usually a G protein-coupled receptor, which activates a G protein. The G protein activates an effector enzyme that makes the second messenger. Adenylyl cyclase converts ATP → cAMP. Phospholipase C splits PIP₂ → IP₃ + DAG. cAMP activates protein kinase A, IP₃ opens Ca²⁺ channels in the endoplasmic reticulum, and DAG with Ca²⁺ activates protein kinase C. One receptor can lead to many second messenger molecules, so the signal is amplified.

On the MCAT: A passage gives a hormone that cannot cross the membrane, such as a peptide hormone or epinephrine. You predict what happens to cAMP, kinase activity or the cell's response if a step is changed. Examples are inhibiting adenylyl cyclase, inhibiting phosphodiesterase (which breaks cAMP down to AMP and ends the signal), or using a G protein stuck in its active form.

Common confusion: The second messenger is not a second hormone, a receptor or a kinase. It is the small molecule or ion made inside the cell. Lipid-soluble steroid hormones typically bind intracellular receptors and alter transcription, so they usually do not need this relay. Blocking the breakdown of a second messenger prolongs the response.

Sources

  • Lehninger Principles of Biochemistry
  • Molecular Biology of the Cell
  • Biochemistry (Berg, Tymoczko, Stryer)

Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.

second messenger: MCAT Glossary