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| to convert to another form |
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utilize intracellular receptors
easily diffuse across the cell membrane, and thus typically bind to intracellular receptors. This messenger-receptor complex then binds to a region of DNA called the hormone response element (HRE)
act as transcription factors
effect of lipophilic messengers is slow to develop in comparison to hydrophilic messengers and its effects typically persis long after the messenger is gone |
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| hormone response element (HRE) |
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Definition
region of DNA located at the beginning of a specific gene.
affects transcription of that gene by either increasing or decreasing its transcription. |
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utilize membrane bound receptors
cannot cross the cell membrane and therefore bind to receptors located on cell membrane. The types of membrane receptors can be categorized in the following manner:
--enzyme linked receptors
--channel linked receptors
--G protein linked receptors |
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[image]
transmembrane receptor that functions as both a receptor and an enzyme.
most are tyrosine kinases
a messenger binds to the membrane receptor, which in turn activates an enzyme on the cytosolic surface. This enzyme catalyzes phosphorylation of an intracellular protein, thereby changing its activity and bringing abouta response in the target cell.
ex: insulin |
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[image]
transmembrane proteins that may act as ion channels.
Activated by the binding of a messenger to the channel which subsequently causes a conformational (allosteric) change of the channel. This typically results in the opening of a channel. Once this channel is opened, ion flow will proceed into or out of the cell, as determined by the electrochemical gradient. |
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| G protein linked receptor |
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Definition
transmembrane receptor associated with a G-protein complex that is located on the cytosolic surface of the cell membrane. the G-protein complex consists of three subunits (alpha, beta, gamma)
When a chemical messenger binds to a G protein linked receptor, the G-protein complex becomes activated. In the active state, the alpha subunit separates and moves to a target protein, causing this target protein to change its activity (G proteins may either activate or inactivate its target)
the target that the alpha subunit interacts with will be either a channel protein or an enzyme |
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[image]
activation of a channel protein by the alpha subunit of the G-protein results in the channel changing conformation, thereby altering ion flow. Channel proteins activated in this manner are called "slow" channels because of the amount of time that passes from the time the messenger binds the membrane bound receptor and the channel eventually opening. This response is relatively slow compared to a "fast" channel protein, which is signaled to alter its conformation immediately by the direct binding of a messenger to a channel receptor. |
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| extracellular chemical messengers utilized to signal between cells. These first messengers bind to a plasma membrane receptor and eventually lead to the presence of a second messenger in the target cell. |
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substances that enter, or are generated in, the cytoplasm as a result of receptor activation by the first messenger
serve as chemical relays from the receptor activated on the plasma membrane to the biochemical machinery of the cell. |
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| enzymes that phosphorylate other proteins by transferring a phosphate group from ATP. This phosphorylation results in altering the conformation/activity of the recipient protein. This recipient protein itself is typically an enzyme. It is typically the phosphorylation of key enzymes at the end of signal transduction pathways that leads to the cell's ultimate biochemical response to the first messenger. |
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the signal transduction system, particularly those using second messengers, allows for small changes in the amount of messenger to result in marked responses from the target cell--this is called signal amplification. A single first messenger molecule results in multiple second messenger molecules. This amplification is accomplished by a cascade of reactions.
the major importance of the second messenger system is its ability to greatly amplify a signal. |
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| a series of sequential reactions that progressively increase in magnitude. |
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various enzymes may be activated via the G-protein complex. When activated, these enzymes catalyze the formation of a product that further amplifies the response to the initial messenger. These enzymes are referred to as amplifier enzymes and include the following:
--adenylate cyclase forms cAMP
--guanylate cyclase forms cGMP
--phospholipase C forms DAG (diacyl glycerol) and IP3 (inositol tripohosphate) |
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| second messenger function (amplifier enzyme products) |
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Definition
cAMP, cGMP, DAG, IP3
the first 3 of these subsequently act by activating specific protein kinases. These protein kinases in turn act to either activate or inactivate another protein.
IP3 utilizes a different mechanism. It binds to channels on smooth endoplasmic reticulum, allowing Ca+2 release into the cytosol. This calcium may act directly on a protein to stimulate contraction or secretion. In addition, calcium ions may also bind to calmodulin. The calcium ion-calmodulin complex then may activate a protein kinase |
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| calcium as a second messenger |
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Definition
[image]
Ca++ is kept at a very low level within the cytosol. This is achieved by active transport systems located in the plasma membrane, as well as within membranes of the smooth endoplasmic reticulum, which is a major storage site for intracellular Ca++. As a result of low cytosolic Ca++ level, there is always a large electrochemical gradient favoring movement of Ca++ into the cytosol, both from the extracellular fluid, as well as from the smooth endoplasmic reticulum.
The concentration of cytosolic Ca++ can be changed by the opening of Ca++ channels in the plasma membrane (allowing diffusion of Ca++ down its electrochemical gradient), as well as by affecting the rate at which Ca++ is actively pumped out of the cell. Finally, cytosolic Ca++ levels can be affected by regulating the release of Ca++ from the smooth endoplasmic reticulum. |
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| Hydrophilic vs. Lipophilic messengers |
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