> [!example]+ Examples of Biological Pathways > - [[Glycolysis & Gluconeogenesis]] > - Immunology > - [[The Alternative Pathway]] > - [[The Classical and Lectin Pathways]] # Biological Signaling A **biological pathway** is a series of actions among molecules in a cell that leads to a certain behavior/new product/change in the cell. ![[Pasted image 20231206210539.png|300]] > [!example]- Signaling Pathways & Logic Gates > Signaling pathways can be thought of as biochemical [[logic gates]]. > > ![[Pasted image 20250311005646.png|350]] ## Principles of Biological Signaling Steps of Cell-to-Cell Communications: 1. **Synthesis** of the signaling molecules by the signaling cell 2. **Release** of the signaling molecule by the signaling cell - Depends on some sort of stimulus (highly varied) 3. **Transport** of the signal of the target cell 4. **Detection** of the signal by a specific receptor protein 5. **Initiation** of one or more signal transduction pathways by the activated receptor 6. **Change in cellular metabolism**, function, or development triggered by the receptor-signal complex 7. **Removal** of the signal, which usually terminates the cellular response --- **Affinity and Dissociation** - When the concentration of L is about equal to Kd, the receptor is about 50% saturated - There is a plateau or exponential drop-off when increasing the ligand concentration past the Kd - This results in the physiological response typically not being strictly parallel in terms of the binding - A very low number of receptors should be occupied when there is no response - i.e. touching a hot surface and having an immediate response --- **Reactions are controlled independently** - The net effect is whichever reaction is doing to most activation and inhibition of other reaction pathways. - Different regulatory proteins/subunits play “hot potato” and bounce back and forth ### Branching Pathways ![[Pasted image 20231019135521.png|300]] Due to the highly organized nature of biological systems, even if molecules are capable of reacting to form trace amounts of byproducts, their concentrations will be insignificant compared to products catalyzed by enzymes. ![[Pasted image 20250311005829.png|300]] Signaling pathways usually have multiple steps and can diverge and/or converge. - *Divergence* allows for multiple responses to a single signal - *Convergence* allows for signal integration and coordination ### Destination of Cellular Signals ![[Pasted image 20230102020950.png|375]] | Type | Description | | :--------------------------------------------------------------: | ------------------------------------------------------------------------------------------ | | Autocrine | A cell targets itself | | Paracrine | A cell targets a nearby cell | | [[Juxtacrine Signaling Example - T Cell and DC.png\|Juxtacrine]] | Cells physically interact through direct contact | | Gap Junctions | A type of endocrine signaling that relies on proteins which form intercellular connections | | Endocrine | A cell targets a distant cell (through the bloodstream) | Because many biological pathways are branching, molecules often end up with multiple different destinations (and can fall under multiple of these classifications as a result. ## Components of Biological Pathways ### Cellular Surface Receptors > See also: > - [[Cells]] > - [[Cellular Compartmentalization]] Cells express arrays of sensing proteins, or **receptors**, that recognize specific extracellular stimuli. It’s important to know how many receptors are on the cell surface when trying to determine the strength of a signal - In cancer, these receptors may be overexpressed (gene amplification) which may cause misleading results when analyzing efficiency ### Signaling Proteins > See also: > - [[Protein Interactions]] **Multiple Isoforms** - Distinct species (isoforms) of similar signaling proteins (ie GPCR) expand the regulatory mechanisms possible in signaling pathways - Isoforms may differ in fucnction, susceptibility to regulation or expression - Cells may express one or several isoforms to fulfill their signaling needs - Gene splicing - One cell may express one or multiple isoforms ### Second Messengers - Provide readily diffiusable pathways for information transfer - Can propagate signals between proteins that are at a distance - cAMP and Ca$^{2+}$ are widely used as second messengers ### Signaling Molecules **Ligand:** A molecule that binds to another specific molecule, in **Lipids & Lipid-Derived Compounds** - Often serve as secondary messengers - Phospholipase Cs release soluble and lipid second messengers in response to diverse inputs - Somewhat reversible process - Channels and transporters are modulated by different lipids in addition to inputs from other sources - PI 3-kinase synthesizes PIP$_3$ to modulate… - Glucose uptake can be promoted by these signaling pathways (cyclical)