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Intracellular Messengers from Phosphatidylinositols The hormone vasopressin is an extracellular signal that activates a specific phospholipase \(\mathrm{C}\) in the membrane. Cleavage of \(\mathrm{PIP}_{2}\) by phospholipase \(\mathrm{C}\) generates two products. What are they? Compare their properties and their solubilities in water, and predict whether either would diffuse readily through the cytosol.

Short Answer

Expert verified
The products are IP3 and DAG. IP3 is water-soluble and diffuses through the cytosol, whereas DAG is hydrophobic and remains in the membrane.

Step by step solution

01

Understanding PIP2 cleavage by Phospholipase C

Phosphatidylinositol 4,5-bisphosphate, abbreviated as PIP2, is a phospholipid found in the cell membrane. When phospholipase C is activated by a signal such as vasopressin, it cleaves PIP2 into two molecules: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
02

Identifying Inositol 1,4,5-trisphosphate (IP3)

IP3 is a hydrophilic molecule due to its three phosphate groups that increase its solubility in water. As a soluble molecule, IP3 remains within the cytosol and can readily diffuse through it to bind to its receptor on the endoplasmic reticulum, facilitating calcium release into the cytosol.
03

Identifying Diacylglycerol (DAG)

DAG is a lipophilic molecule and more hydrophobic in nature, as it contains two fatty acid chains from the PIP2 molecule. Thus, DAG remains within the lipid bilayer of the membrane and does not diffuse through the aqueous cytosol readily.
04

Comparing Solubilities and Diffusion

Comparing the properties of IP3 and DAG, IP3 is water-soluble and diffuses through the cytosol easily, carrying the signal further. On the other hand, due to its hydrophobic nature, DAG stays within the cell membrane and does not diffuse readily through the cytosol.

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Key Concepts

These are the key concepts you need to understand to accurately answer the question.

Phosphatidylinositols
Phosphatidylinositols are a group of lipids that play crucial roles in cellular signaling. They are a unique component of the cell membrane, serving as precursors for several intracellular signaling molecules. These molecules consist of a glycerol backbone, two fatty acid tails, and an inositol ring bonded through a phosphate group. The inositol ring can be phosphorylated at different positions, producing various phosphoinositides that are key in signal transduction pathways.

In the context of intracellular signaling, phosphatidylinositols are vital because they can be modified by enzymes to generate second messengers, which help convey signals from outside the cell to the cell's interior. They are particularly important in processes such as cell growth, survival, and metabolism.
Phospholipase C
Phospholipase C (PLC) is an essential enzyme in the signal transduction pathway. It acts by hydrolyzing phosphatidylinositols, specifically phosphatidylinositol 4,5-bisphosphate (PIP2), creating two significant second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).

Phospholipase C is activated by several extracellular signals, such as hormones and neurotransmitters, that bind to surface receptors and recruit PLC to the membrane. This enzyme then cleaves PIP2 at the inositol head group, producing IP3 and DAG. These molecules have distinct roles in further signaling within the cell. The activity of PLC is crucial for the propagation of signals within the cell, leading to various cellular responses.
PIP2
PIP2, or phosphatidylinositol 4,5-bisphosphate, is a minor yet vital component of the plasma membrane. Despite its small quantity, PIP2 plays a significant role in cell signaling. It serves as a substrate for multiple enzymes, including phospholipase C, which cleaves it to generate IP3 and DAG.

PIP2's structure includes a glycerol backbone, two fatty acid tails, and a phosphatidylinositol head with phosphates at the 4th and 5th positions of the inositol ring. This arrangement allows it to participate in signaling pathways that control a range of biological activities, such as ion channel regulation and cytoskeleton organization. PIP2 is a pivotal molecule that bridges extracellular signals to intracellular effects.
Inositol 1,4,5-trisphosphate (IP3)
Inositol 1,4,5-trisphosphate (IP3) is a polar, water-soluble molecule derived from the cleavage of PIP2 by phospholipase C. Due to its three phosphate groups, IP3 is highly hydrophilic and can diffuse easily through the cytosol.

IP3's primary role in cellular signaling involves the release of calcium ions from the endoplasmic reticulum into the cytosol. When IP3 binds to its specific receptor on the endoplasmic reticulum, it opens calcium channels, increasing calcium concentrations in the cytosol. This calcium release triggers various physiological responses, including muscle contraction, secretion, and metabolic regulation.
Diacylglycerol (DAG)
Diacylglycerol (DAG) is a lipophilic molecule formed alongside IP3 when phospholipase C cleaves PIP2. Unlike IP3, DAG is non-polar due to its two long fatty acid chains, which remain embedded within the plasma membrane.

Rather than diffusing through the cytosol, DAG stays within the lipid bilayer, where it functions to activate protein kinase C (PKC). This activation leads to various downstream signaling effects, such as cell proliferation and differentiation. DAG serves as a membrane-bound component in intracellular signaling cascades, playing a role distinct from its cytosolic counterpart, IP3.
Cytosolic Signal Diffusion
Cytosolic signal diffusion is a crucial aspect of intracellular signaling, allowing molecules to relay and amplify signals effectively within the cell. When signaling molecules like IP3 are formed, they travel through the cytosol to reach and activate their target sites.

The high solubility of IP3 in water facilitates its rapid diffusion, enabling it to quickly bind to receptors and initiate a response. This is contrasted with molecules like DAG, which remain within the membrane and require different mechanisms to propagate signals. Efficient cytosolic diffusion ensures that signals are transmitted over distances within the cell swiftly and accurately, leading to timely cellular responses.

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Most popular questions from this chapter

Deducing Lipid Structure from Molar Ratio of Components Complete hydrolysis of a glycerophospholipid yields glycerol, two fatty acids \(\left(16: 1\left(\Delta^{9}\right)\right.\) and \(\left.16: 0\right)\), phosphoric acid, and serine in the molar ratio \(1: 1: 1: 1: 1\). Name this lipid and draw its structure.

Characteristics of Lipid Transport Proteins Often when lipids are transported between different tissues, they are carried by proteins. In this exercise, you will explore the interactions between a lipid and a protein using the PDB (www.rcsb,org). Use the PDB identifier 2YG2 and study the structure of the complex between HDL-associated apolipoprotein \(\mathrm{M}\) and sphingosine-1-phosphate. Navigate to 3D View: Structure to answer the following questions. a. What protein motif is adopted by apolipoprotein M? b. Which amino acid residues do you find lining the sphingosine binding pocket? What do they have in common? c. The phosphoryl group of sphingosine-1-phosphate is exposed on the surface of the protein. Why do you suppose it is important that the transport protein binds the hydrocarbon tail of sphingosine-1-phosphate but not necessarily the polar head group?

Using the LIPID MAPS Database to Find Solubility Information Lipidomics has identified thousands of cellular lipids. LIPID MAPS is an online database containing over 40,000 unique lipid structures, as well as information on the chemical and physical properties of each lipid (www.lipidmaps.org). One important parameter when working with lipids is \(\log P\), where \(P\) is the octanol:water partition coefficient, an indicator of lipophilicity. a. Look up cholesterol, sphingosine, linoleic acid, and stearic acid in LIPID MAPS and use the reported \(\log P\) values to place them in order of increasing solubility in octanol. b. Pharmacologists often study \(\log P\) values when developing new drugs. Why would knowing a drug's \(\log\) \(P\) value be informative?

Melting Points of Lipids The melting points of a series of 18-carbon fatty acids are stearic acid, \(69.6^{\circ} \mathrm{C}\); oleic acid, \(13.4^{\circ} \mathrm{C}\); linoleic acid, \(-5{ }^{\circ} \mathrm{C}\); and linolenic acid, \(-11{ }^{\circ} \mathrm{C}\). a. What structural aspect of these 18-carbon fatty acids can be correlated with the melting point? b. Draw all the possible triacylglycerols that can be constructed from glycerol, palmitic acid, and oleic acid. Rank them in order of increasing melting point. c. Branched-chain fatty acids are found in some bacterial membrane lipids. Would their presence increase or decrease the fluidity of the membrane (that is, give the lipids a lower or a higher melting point)? Why?

Structure of an Omega-3 Fatty Acid The omega-3 fatty acid docosahexaenoic acid (DHA, \(\left.22: 6\left(\Delta^{4,7,10,13,16,19}\right)\right)\) is the most abundant omega-3 fatty acid in the brain and an important component of breast milk. Draw the structure of this fatty acid.

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