Systems Biology
Peptide hormones are hormones made of amino acid chains, ranging in size from small molecules like oxytocin to larger ones such as insulin. They begin as long polypeptide chains called preprohormones, which are synthesized directly into the rough endoplasmic reticulum (ER) by ribosomes. Inside the lumen of the rough ER, preprohormones are cleaved by enzymes into smaller prohormones, inactive precursors of peptide hormones. Prohormones pass into the Golgi apparatus for further processing, where they are packaged into vesicles and cleaved by enzymes into smaller active peptide hormones. These vesicles then fuse with the cell's plasma membrane, and the active peptide hormones are released from the cell via exocytosis.
Peptide hormones are polar and hydrophilic, allowing them to circulate in the bloodstream without the help of carrier proteins. However, their polarity prevents them from crossing the plasma membrane of their target cells. Instead, they bind to target cell surface receptors, initiating second messenger cascades and signal amplification. Some of the most common peptide hormone receptors are G-protein-coupled receptors (GPCRs), which activate G-proteins and a range of second messenger cascades, depending on the type of alpha subunit. Notable pathways include those involving cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers relay and amplify signals from peptide hormones, ultimately modulating gene expression and cellular function.
Lesson Outline
<ul> <li>Peptide hormones are made of amino acid chains (examples include oxytocin and insulin)</li> <li>Synthesis of peptide hormones: <ul> <li>Begins as preprohormones in the rough endoplasmic reticulum (ER) synthesized by ribosomes.</li> <li>Cleaved by enzymes into smaller prohormones in the rough ER lumen.</li> <li>Prohormones pass into the Golgi apparatus for further processing.</li> <li>Golgi apparatus packages prohormones in vesicles and cleaves them into active peptide hormones.</li> <li>Vesicles fuse with the cell's plasma membrane, and peptide hormones are released via exocytosis.</li> </ul> </li> <li>Secretion of peptide hormones: <ul> <li>Constitutive secretion: Some peptide hormones are exocytosed as they're produced.</li> <li>Regulated secretion: Most peptide hormones are stored in the cell and released in bursts when signaled.</li> </ul> </li> <li>Travel in the bloodstream: <ul> <li>Peptide hormones are polar and hydrophilic, thus don't need carrier proteins to move through the blood (because blood is also polar).</li> <li>Peptide hormones have a short half-life, lasting only a few minutes in the bloodstream; thus, they must be constantly replenished.</li> </ul> </li> <li>Action on target cells: <ul> <li>Peptide hormones bind to surface receptors on target cells, activating a signal cascade.</li> <li>Signal cascades involve first messengers (peptide hormones) and second messengers (intracellular molecules).</li> <li>Signal amplification occurs as a single hormone can bind multiple receptors and initiate multiple cellular actions.</li> </ul> </li> <li>Two common peptide hormone pathways: <ul> <li>Both pathways start with G protein-coupled receptors (GPCRs).</li> <li>When a peptide hormone binds its GPCR, it activates the G-protein complex (G-protein complex = 3 subunits (alpha, beta, and gamma)) .</li> <li>Activated G-proteins exchange GDP for GTP and separate into alpha subunit with GTP, and a beta and gamma subunit complex.</li> </ul> </li> <li>Three common and important forms of alpha subunits: <ul> <li>Gs protein alpha subunit: Activates adenylyl cyclase, an enzyme that converts ATP to cAMP <ul> <li>cAMP can activate protein kinase A (cAMP-dependent kinase that binds phosphate groups to proteins) and phosphorylate CREB (a transcription factor that regulates various cellular responses).</li></ul> <li>Gi protein alpha subunit: Inhibits adenylyl cyclase and cAMP production, dampening the cellular response.</li> <li>Gq protein alpha subunit: Activates phospholipase C (an enzyme that cleaves membrane phospholipids), which generates DAG and IP<sub>3</sub> (second messengers). These activate calcium-dependent enzymes and release calcium ions from the ER.</li> </ul> </li> <li>Naming convention for eptide hormones: <ul> <li>Typically end in "in" for direct hormones (e.g., oxytocin, prolactin).</li> <li>Trophic hormones signal other endocrine glands and may include words like "releasing" or "stimulating."</li> </ul>
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FAQs
Peptide hormone synthesis consists of several steps, starting from the translation of mRNA into a preprohormone. The preprohormone is then cleaved to form a prohormone, which undergoes further processing within the endoplasmic reticulum and Golgi apparatus to generate an active peptide hormone. Finally, the mature peptide hormone is secreted via exocytosis and can interact with its target cells to trigger a response.
Preprohormones and prohormones are precursors to mature peptide hormones. Preprohormones are the initial products of translation that contain a signal peptide sequence, the prohormone, and sometimes an additional peptide sequence. The signal peptide ensures that the preprohormone is transported into the endoplasmic reticulum for further processing. Once the signal peptide is cleaved, the remaining molecule is called a prohormone, which undergoes further modifications before it becomes a biologically active hormone.
Peptide hormones are hydrophilic molecules, meaning they are soluble in water and cannot easily diffuse across the lipid bilayer of the cell membrane. Exocytosis is a process that allows cells to secrete these large, hydrophilic molecules by enclosing them in vesicles and fusing the vesicles with the plasma membrane. This enables the hormones to be released into the extracellular environment without having to cross the plasma membrane.
Peptide hormones serve as first messengers, which are signaling molecules that initiate a signal cascade by binding to specific cell surface receptors on target cells. This binding event triggers a conformational change in the receptor and activates intracellular signaling pathways. These pathways often involve second messengers, such as cyclic AMP (cAMP) or calcium ions, that amplify the signal and transmit it to effector proteins, ultimately resulting in a cellular response.
G protein-coupled receptors (GPCRs) are cell surface receptors commonly involved in the signaling of peptide hormones. When a hormone binds to its specific GPCR, a conformational change occurs that activates an associated G protein. The activated G protein can then interact with other signaling proteins, such as adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP); cAMP acts as a second messenger to propagate and amplify the hormonal signal within the cell, ultimately leading to various cellular responses.
