1. Chapter 5 Chemical Messengers
Mechanisms of Intercellular Communication 細胞間溝通的機制
Chemical Messengers 化學訊息傳導物
Signal Transduction Mechanisms 訊息傳遞機制
Long-Distance Communication via the Nervous and Endocrine Systems 經由神經及內分泌細胞做長距離的溝通

2. I. Mechanisms of Intercellular Communication
Virtually all body functions require communication 溝通 between cells
In relatively few instances cells are physically linked by gap junctions 空隙聯合; in most instances cell communicate through chemical messengers 化學訊息傳導物
Direct Communication Through Gap Junctions
Indirect Communication Through Chemical Messengers
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3. Direct Communication Through Gap Junctions
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Figure 5.1 Types of intercellular communication. (a) Direct communication through gap junction. Gap junctions are composed of membrane protein structures called connexons that link the cytosols of two adjacent cells, allowing ions and small molecules to move between cells.
The movement of ions through gap junctions electrically couples the cells, such that electrical signals in one cell are directly transmitted to the neighboring cells  for example, in heart muscle, smooth muscle
The movement of small molecules through gap junctions metabolically couples the cells, such that one cell can provide necessary nutrients to other cells  for example, in bone cells P

4. Indirect Communication Through Chemical Messengers
Figure 5.1 Types of intercellular communication. (b) Communication via chemical messengers. After a secretory cell 分泌細胞 releases a messenger 訊息物 into the extracellular fluid, the messenger binds to receptors 接受器 on target cells 目標細胞, triggering a response in the target cell
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Most often, cells communicate via chemical messengers, which are all ligands 結合物, molecules that bind to proteins reversibly
A target cell responds to the chemical messenger because it has certain proteins, called receptors 接受器, that specifically recognize and bind the messenger
The binding of messengers to receptors produces a response in the target cell through a variety of mechanisms referred to as signal transduction
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5. II. Chemical Messengers
Functional Classification 功能分類 of Chemical Messengers
Chemical Classification 化學分類 of Messengers
Synthesis and Release 合成及釋放 of Chemical Messengers
Transport 運送 of Messengers

6. Functional Classification of Chemical Messengers
Chemical messengers can be classified on the basis of their function 功能 and chemical structure 化學結構
Although there are hundreds of chemical messengers, most can be classified into four main categories:
Paracrines 旁泌素
Autocrines 自泌素
Neurotransmitters 神經傳導物質
Hormones 賀爾蒙
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7. Paracrine & Autocrine P127-128
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Figure 5.2 Functional classes of chemical messengers. (a) Paracrines are secreted by one cell and diffuse to a nearby target cell. (b) Autocrines bind to receptors on the cell that secreted them.
Paracrines generally include growth factors 生長因子, clotting factors 凝血因子, and cytokines 細胞激素  growth factors are proteins that stimulate proliferation 增生 and differentiation 分化 of cells; clotting factors are proteins that formation of a blood clot 血塊; cytokines are peptides, usually released from immune cells 免疫細胞, that function in coordinating the body’s defense against infection 一同對抗感染
Autocrines are similar to paracrine, except that autocrines act on the same cell that secreted them P

8. Neurotransmitters & Hormones
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Figure 5.2 Functional classes of chemical messengers. (c) Neurotransmitters are secreted from neurons at functionally specialized structures call synapses 突觸. The axon terminal of a presynaptic cell 突觸前細胞 releases the neurotransmitter, which then diffuses a very short distance to bind to receptors on a very specific target cell called the postsynaptic cell 突觸後細胞. (d) Hormones are secreted by endocrine cells into the interstitial fluid. Hormones then diffuse into bloodstream for transport to target cells in the body. Target cells are identified by the presence of receptors for the specific hormone. Cells without receptors for the hormone cannot respond to the hormone’s signal.
Neurohormones 神經賀爾蒙 are a special class of hormones secreted by neurons  like hormones, they are secreted into the interstitial fluid and then diffuse into the blood for transport to target cells throughout the body P

9. Functional Classification of Chemical Messengers
An example of a paracrine messenger is histamine 組織胺, a chemical that is important in allergic reactions 過敏反應 and inflammation 發炎 and is secreted by mast cells 肥胖細胞 scattered throughout the body
Histamine is a biogenic amine 生物性胺類 with paracrine, autocrine, and neurotransmitter functions
It is important to realize that one chemical messenger may fit more than one of these functional classes  ex. histamine, serotonin P
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10. Chemical Classification of Messengers
A messenger’s chemical structure 化學結構 determines its mechanisms of synthesis, release, transport and signal transduction
The most important chemical characteristic is whether the messenger can dissolve in water or cross the lipid bilayer in the plasma membranes
Lipophilic 親脂性 (hydrophobic 疏水性)  can cross plasma membrane
Hydrophilic 親水性 (lipophobic 舒脂性)  can dissolve in plasma or ISF
The five major classes of chemical messengers:
Amino acids 胺基酸
Amines 胺類
Peptides/proteins 胜肽/蛋白質
Steroids 類固醇
Eicosanoids
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11. Summarize of Chemical classification of Messengers
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12. Peptide/Protein Messengers
Amino Acid Messengers
Four amino acids are classified as chemical messengers because they function as neurotransmitters in the brain 腦 and spinal cord 脊髓  glutamate; aspartate; glycine; GABA (gamma-amino butyric acid)
Amino acids are lipophobic (hydrophilic) 親水性 they dissolve in water 溶於水 but do not cross plasma membrane 不能穿越細胞膜
Peptide/Protein Messengers
Most chemical messengers are polypeptides 多胜肽, chains of amino acids linked together by peptide bonds
These messengers are classified as peptides or proteins based on their size  peptides (< 50 amino acids), proteins (> 50 amino acids)
Polypeptides are lipophobic  dissolve in water but cannot cross plasma membranes
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13. Amine Messengers
Amines, which are chemical messengers derived from amino acids, are so named because they all posses an amine group (-NH2)
Catecholamines 兒茶酚胺—contain a catechol 兒茶酚 group & derived from tyrosine
Dopamine 多巴胺  neurotransmitter
Norepinephrine 正腎上腺素  neurotransmitter
Epinephrine 腎上腺素  hormone
Serotonin 血清胺—derived from tryptophan  neurotransmitter
Histamine 組織胺—derived from histidine  paracrine
Thyroid hormones 甲狀腺素—derived from tyrosine  hormone
Most of the amines are lipophobic, but the thyroid hormones are lipophilic
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14. Steroid Messengers Eicosanoids
Steroids are a class of compounds derived from cholesterol 膽固醇  all steroid messengers function as hormones
Because steroids are derived from cholesterol, which is lipophilic 親脂性, they too are lipophilic and readily cross plasma membrane 容易穿越細胞膜 and are insoluble in water 不溶於水
Eicosanoids
Most eicosanoids are derived from arachidonic acid 花生四烯酸, a 20-carbon fatty acids that is found in various plasma membrane phospholipid  include prostaglandins, leukotrienes, and thromboxanes
Because eicosanoids are lipids, they readily cross plasma membrane and are insoluble in water
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15. Synthesis and Release of Chemical Messengers
Synthesis 合成 depends on chemical class
Release 釋放 of chemical messengers
Lipophilic messengers  diffusion 擴散
released upon synthesis 合成後立即釋放
regulate release by regulating rate of synthesis 藉由調控合成速率來調控釋放
Lipophobic messengers  exocytosis 胞吐
stored in vesicles prior to release 釋放前先儲存在小泡中
regulate rate of exocytosis 藉由調控胞吐的速率來調控釋放
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16. Amino Acids
Although amino acids can be obtained from the diet, the four amino acids that function as neurotransmitters must be synthesized within the neuron that will secrete them 在欲分泌的神 經細胞內合成
Following their synthesis in the cytosol 在細胞質合成, amino acid neurotransmitters are transported into secretory vesicles where they are stored until they are released by exocytosis
20 alpha amino acids in body (used in proteins)
9 are essential 必須的 (身體不可以合成); 11 can be synthesized in body 身體可以合成
3/11 are neurotransmitters (glutamate, aspartate, glycine)
1 gamma amino acid (GABA) = neurotransmitter
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17. Amines
All amines are derived from amino acids, all are synthesized in cytosol by sequence of enzyme catalyzed reactions (except thyroid hormones)
Note that in this pathway, dopamine is the precursor 前驅物 for norepinephrine, which in turn serves as the precursor for epinephrine
Following synthesis, amines are packaged into cytosolic vesicles, where they are stored until their release is triggered  release occurs by exocytosis
Figure 5.3 Catecholamine synthesis. Catecholamines are synthesized from the amino acid tyrosine by a sequence of enzyme-catalyzed reactions in which one catecholamine functions as the precursor for the next. The names of catecholamines that function as messengers are highlighted 強調.
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18. Peptides and Proteins P131-132
Peptides and proteins are synthesized in the same way as other proteins destined for secretion
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副甲狀腺賀爾蒙
Figure 5.4 Peptide synthesis and release. P

19. Steroids
Steroid messengers are synthesized from cholesterol in a series of reactions catalyzed by enzymes located in the smooth ER or mitochondria 位於平滑內質網或 粒線體上的酵素所催化的反應
Because steroids are membrane- permeant 膜可滲透, they are synthesized on demand and released immediately 依需求而 合成且立即釋放
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Adrenal cortex
腎上腺皮質
Figure 5.5 Synthetic pathway for steroids. Each arrow indicates an enzyme-catalyzed reaction 酵素催化的反應. Green boxes indicate hormones produced in the adrenal cortex 腎上腺皮質; blue boxes indicate male sex hormones; orange indicate female sex hormones
Testes 睪丸
Ovary 卵巢 P

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Eicosanoids
Like steroids, eicosanoids are synthesized on demand and released immediately because they are lipophilic and able to pass through plasma membranes easily
Figure 5.6 Eicosanoid synthesis. Phospholipase A2 catalyzes the conversion of a membrane phospholipid to arachidonic acid, the precursor for all eicosanoids. Arachidonic acid is converted into eicosanoids via two pathways: The cyclooxygenase-dependent pathway leads to the production of prostaglandins, prostacyclins, and thromboxanes, whereas the lipoxygenase-dependent pathway leads to the production of leukotrienes.
Prostacyclins and thromboxanes are important in blood clotting 血液凝固; prostaglandins are involved in several systems, including the inflammatory response 發炎反應
Leukotrienes also contribute to the inflammatory response P

21. Transport of Messenger
In many instances, the messenger is released from a cell that is near the target cell, such that the messenger reaches the receptor by simple diffusion  paracrines; autocrines; most cytokines; neurotransmitters
Typically these messengers are quickly degraded in the interstitial fluid and became inactive, minimizing the spread of their signaling 這種訊息物通常在間質液很快被分解成沒有活性的代謝物，以減少其 訊息擴散出去
Hormone are transported in the blood and thus have access to most cells in the body  hormones; neurohormones; some cytokines
Hormones can be transported in the blood either in dissolved form 溶解態 (hydrophilic 親水性 messengers) or bound to carrier proteins 結合態 (hydrophobic 疏水性 messengers)
hydrophilic 親水性 messengers  amines, peptides/proteins
hydrophobic 疏水性 messengers  steroids, eicosanoids, thyroid hormone P

22. Transport of Messengers
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Figure 5.7 Transport of messenger in blood (a) Hydrophilic messengers, such as peptides and amines, are secreted by exocytosis, enter the bloodstream, and dissolve in the plasma. (b) Hydrophobic messengers are secreted by simple diffusion and then enter the bloodstream. Most of the messenger molecules are transported bound to carrier proteins. Only the small amount of free hormone in the plasma is immediately available binding with target cell receptors.
Some carrier proteins are specific for a particular hormone, such as corticosteroid-binding globulin (CBG) for cortisol
Other carrier protein—for example, albumin—are not specific and can transport many different hormones
Hormones that are present in dissolved form have relatively short half-lives 半衰期短, usually minutes
Hormones that are bound to carrier proteins are protected from degradation and have longer half-lives 半衰期長, generally hours
Half-life: time it takes for half of the hormone in blood to be degraded P

23. III. Signal Transduction Mechanisms
Chemical messengers transmit their signals by binding to target cell receptors located either on the plasma membrane 細胞膜, in the cytosol 細胞質液, or in the nucleus 細胞核
The location of the receptor depends on whether the messenger is lipophilic or lipophobic
Properties of Receptors
Intracellular Receptor-Mediated Responses
Membrane-bound Receptor-Mediated Responses
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24. Properties of receptors
Receptors shows specificity 專一性 for messenger  they generally bind only one messenger or a class of messengers 一種接受器通常只會與一種或一大類的傳導物結合
The binding between a messenger and receptor is a brief, reversible chemical interaction 傳導物與接受器的結合通常是短暫、可逆的化學反應
The strength of the binding between a messenger and its receptor is termed affinity 傳導物與接受器結合的強度稱為親和力
Figure 5.8 Receptor specificity. Receptor A is specific for messenger 1, receptor C is specific for messenger 2, and neither messenger can bind to receptor B. Note that receptors can be located either on the plasma membrane (A & B) or inside the cell (receptor C).
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25. Properties of receptors
Adrenergic receptors  catecholamine (dopamine, epinephrine, norepinephrine)
Properties:
Specificity of receptor to messenger  bind only one messenger or a class of messengers
Often more than one type of receptor for one messenger
One cell may different have receptors for different messengers, or even types of receptors for one messenger
A single messenger can often bind to more than one type of receptor, and these receptors may have different affinities 不同親和力 for the messengers  epinephrine (adrenaline) and norepinephrine (noradrenaline) can bind to adrenergic receptors (a1, a2, b1, b2, b3)  for a receptors: epinephrine = norepinephrine  for b2 receptors: epinephrine > norepinephrine
A single target cell may have receptors for more than one type of messenger  skeletal muscle cells have receptor for acetylcholine and insulin
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26. The relationship between receptor binding and the magnitude of the target cell response
As a general rule, the magnitude of a target cell’s response 目標 細胞反應的大小 to a chemical messenger depends on three factors:
the messenger’s concentration 傳導物的濃度
the number of receptors present 接受器的數目
the affinity of receptor for messenger 傳導物與接受器結合的親和力
 M (messenger)  + R (receptor)  M-R complex   Response 
Figure 5.9 Effect of messenger concentration on messenger-receptor binding. The proportion of receptors bound increases as the concentration of messenger increases. Because the amount of bound receptor determines the magnitude of target cell response, the y-axis could also have been labeled “target cell response.”
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27. The relationship between receptor binding and the magnitude of the target cell response
The target cell’s response also depends on the number of receptor it possesses 目標細胞所擁有的接受器數目
M (messenger) +  R (receptor)   M-R complex   Response 
Figure 5.10 Effect of receptor concentration and affinity on messenger-receptor binding. (a) Effects of receptor density. The two curves illustrate the effects of doubling the concentration of a given receptor on a target cell. R refers to a given concentration of the receptor, whereas 2R refers to twice that concentration of that receptor. When the receptor concentration doubles, the maximum number of receptors that can bond with messenger also doubles.
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28. The relationship between receptor binding and the magnitude of the target cell response
The target cell’s response also depends on the affinity of its receptor for the messenger 接受器與傳導物結合的親和力
M (messenger) + R (receptor)   M-R complex   Response 
Figure 5.10 Effect of receptor concentration and affinity on messenger-receptor binding. (b) Effects of receptor affinity. The two curves illustrate the effects of receptor affinity on the proportion of receptors with messenger bound to them. At any concentration of messenger below saturation, a higher proportion of high-affinity receptors have bound messenger compared to low-affinity receptors. The high-affinity receptors reach saturation at a lower messenger concentration than do the low-affinity receptors. Note that the maximum number of sites that can be bound is independent of receptor affinity 接受器被飽和(達最大結合量)與親和力不相關
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29. Up and Down Regulation of Receptors
The number of receptors that a target cell possesses can vary under different circumstances as a result of the synthesis of new receptors or turnover of old receptors 目標細胞擁有的接受器數目會在不同情況下 有所改變，可藉由合成新的接受器或將舊的接受器代謝而增加或減少接受器 的數目
Up-regulation, an increases in the number of receptors compared to “normal” condition, occurs when cells are exposed to low messenger concentrations for a prolonged period 當細胞長期暴露在低濃度的傳導物之下，細胞會藉由增加接受器的數目來 適應此狀況，此稱為接受器的上調節作用
By producing more receptors, target cells adapt to the relative lack of messenger by becoming more responsive to it 因為產生較多的接受器， 目標細胞會對此低濃度的傳導物敏感性增加而適應之
Down-regulation, a decrease in the number of receptors, occurs when messenger concentrations are higher than normal for a prolonged period 反之，當長期暴露在高濃度的傳導物之下，細胞可藉由降低接受器 數目而適應之，稱為接受器的下調節作用
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30. Receptor Agonists and Antagonists
Although target cell responses are always triggered by receptor binding, it is not true that receptor binding always triggers a response 並不是結合物與接受器結合都會誘導反應產生
Ligands that bind to receptors and produce a biological response are called agonists 作用劑；致效劑, whereas antagonists 拮抗劑 are ligands bind to receptors do not produce a response
Instead, antagonists may actually complete with agonists for the receptor, decreasing the likelihood that the binding of agonist to receptor will occur and bring about a response 拮抗劑可與作用劑競爭 而降低作用劑與接受器結合的機會，使其不產生反應
Norepinephrine is an endogenous ligands 內生性結合物 binding to an a receptor  phenylephrine is an a agonist and exerts the same effects, however, phenoxybenzamine is an a antagonist and prevents norepinephrine from binding to a receptor
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31. Signal transduction mechanisms for responses mediated by intracellular receptors
Receptors for lipophilic messengers are usually located in the cytosol or nucleus of target cells and are readily accessible because these messengers easily permeate the plasma membrane 脂溶性傳導物的接受器通常位於細胞質或細胞核內，因傳導物很容易 進入細胞膜而接近接受器
The binding of the messenger to the receptor alters the synthesis of a specific protein  changes in protein synthesis can take hours or even days, effects of lipophilic messengers are generally slow to develop 脂溶性傳導物與接受器結合後會影響蛋白質合成，由於蛋白質 的合成需要一段時間，因此脂溶性傳導物的反應比較慢發生
In addition, because these newly synthesized proteins often remain in the target cells long after the messenger is gone, the effects can persist a long time 此外，當傳導物離開後，由於期促進合成的蛋白 質還在細胞內產生作用，因此其反應還可維持一段時間 P

32. P137 Figure 5.11 Actions of lipophilic messengers on target Cell.
a. When receptors are in the nucleus, the hormone diffuses into the nucleus and binds to the receptor, forming a hormone- receptor complex in the nucleus
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b. When receptor are in the cytosol, the hormone binds to the receptor there, forming a hormone-receptor complex that then moves into the nucleus
The hormone-receptor complex binds to the hormone response element (HRE), which is located at the beginning of a specific gene   activating (or deactivating) a gene  mRNA is transcribed in the nucleus
mRNA moves from the nucleus into the cytosol through nuclear pores
mRNA is translated by ribosomes to form proteins  response
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33. Signal transduction mechanisms for responses mediated by membrane-bound receptor
Lipophobic messengers cannot permeate the plasma membrane to any significant degree and thus their receptors are located on the plasma membrane and face the extracellular fluid 親水性的傳導物無物法穿越細胞膜，因此接 受器位於細胞膜上，面向細胞外液
The receptors for these messengers fall into three general categories:
Channel-linked Receptors
Enzyme-linked Receptors
G-Protein-linked Receptors
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34. Channel-linked Receptors
Voltage-gated channel
Ion channels that open or close in response to the binding of a chemical to a receptor or to the channel are called ligand-gated channels 因結合物結合而使接受器(通道)打開或關閉的離子通道稱為 結合物-閘門通道
Channel-linked receptors are a type of ligand-gated channel in which the ligand is a messenger that binds to a receptor
These channels fall into two categories:
Fast channels–the receptor and channel are the same protein
Slow channels–the receptor and channel are separate protein but are coupled together by a third type of protein, called G protein
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35. Fast ligand-gated channels
Figure 5.12 Fast ligand-gated channels and how they change the electrical properties of cells. Binding of a messenger to the receptor/channel opens the ions channel. The opening of most ion channels results in movement of ions into or out of the cell, which changes the electrical properties of the cell.
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Because the binding of messenger to receptor is brief, and the channel is open only while the messenger is bound, the change in membrane potential does not usually last long and terminates in a few milliseconds
For example, the neurotransmitter acetylcholine stimulates skeletal muscle contraction by binding to nicotinic receptor, which is sodium channel
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36. Fast ligand-gated channels
Figure 5.13 Fast ligand-gated calcium channels. Binding of a messenger to the receptor/channel opens calcium channel, enables calcium ions to enter the cell. Calcium entry will  change the electrical properties 改變細胞的電性of the cell, but calcium also trigger a variety of responses such as a  secretion of some product by exocytosis, muscle contraction, or  change in activity of a protein. In the last instance, calcium  acts as a second messenger, binding to the protein calmodulin to form a calcium-calmodulin complex  the complex activates a protein kinase, which phosphorylates a protein that produces a response in the cell.    
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37. Calcium Levels in Cytosol
Calcium is well suited for its role in intracellular signaling because it is normally present in very low concentrations in the cytosol (10-7 – 10-6 M), as compared to 10-3 M in extracellular fluid
The significance of this low cytosolic concentration of calcium is that entry into a cell of even a small quantity of calcium causes a relatively large percentage change in the concentration, which means that the system is sensitive
Intracellular calcium levels are maintained at their normal low levels by three processes:
active transport across plasma membrane
sequestration by binding with proteins in cytosol
active transport into smooth endoplasmic reticulum or mitochondria
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38. Enzyme-Linked Receptors
Enzyme-linked receptors function both as enzymes and as receptors  are transmembrane proteins, with the receptor side facing the interstitial fluid and the enzyme side facing the cytosol
Most enzyme-linked receptors are tyrosine kinases, other are guanylate cyclases, which catalyze the conversion of GTP to the second messenger cGMP
These enzymes are normally inactive but are activated when a messenger binds to receptor, which allows them to catalyze intracellular reactions
A messenger binds to the receptor, changing its conformation   the conformation change activates the tyrosine kinase
The tyrosine kinase then catalyzes phosphorylation of an intracellular protein   phosphorylation of the protein changes its activity by covalent modulation, bringing about a response in the target cell
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Figure 5.14 An enzyme-linked receptor.

39. G Protein Linked Receptors
G protein-linked receptors works by activating special membrane proteins called G proteins
G protein are located on the intracellular side of the plasma membrane, where they function as links between the G protein- linked receptor and other proteins in the plasma membrane, such as ion channels or enzymes
G proteins, which get their name from their ability to bind guanosine nucleotides, have three subunits: alpha (a), beta (b), and gamma (g)
G proteins are a diverse group  functionally, G proteins can be classified into three basic types:
those that affect ion channels  slow ligand-gated ion channels
stimulatory G proteins (Gs)  activation of enzymes  production of second messengers 次級訊息傳導物
inhibitory G proteins (Gi)  inhibition of enzymes  reduction of second messengers
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40. Slow ligand-gated ion channel
Figure 5.15 Action of a G protein on a slow ligand-gated ion channel.  Binding of a messenger to a G-protein-linked receptor activates the G protein.  The alpha subunit moves to an ion channel in the membrane.  The ion channel opens or closes, changing the permeability of the membrane to a specific ion. The movement of ions across the plasma membrane is altered, changing the electrical properties of the cell.
activate
inactivate
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There are two important differences between the fast and slow ligand-gated channels:
At fast ligand-gated channel, messenger bind to receptor only opens the channel; G protein-linked receptor can be either opened or closed by messenger binding to the receptor
Binding of a messenger to channel-linked receptor produces an immediate and brief (only a few milliseconds) response in the target cell; G protein-linked receptor are slow and stay open or closed for long periods, often minutes
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41. G Protein Linked Receptors
G protein-regulated enzymes are associated with the production of second messengers in the cytosol
Five major second messengers account for most of the communication through G-protein-regulated enzymes:
cAMP (cyclic adenosine monophosphate)
cGMP (cyclic guanosine monophosphate)
Inositol triphosphate (IP3)
Diacylglycerol (DAG)
Calcium
First
messenger
Second
messenger
Response
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42. cAMP second messenger system
The first messenger binds to the receptor, activating a Gs protein
The G protein releases the a subunit, which binds to and activates the enzyme adenylate cyclase
Adenylate cyclase catalyzes the conversion of ATP to cAMP
cAMP activates protein kinase A, also called cAMP-dependent protein kinase
The protein kinase catalyzes the transfer of a phosphate group from ATP to a protein, thereby altering the protein’s activity
Altered protein activity causes a response in the cell
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Figure 5.16 The cAMP second messenger system. P

43. Termination of cAMP second messenger system
Termination of the actions 作用終止 of cAMP requires its degradation by the enzyme cAMP phosphodiesterase (PDE)
cAMP (activate) AMP (inactivate)
For the actions of the phosphorylated protein to be terminated, the phosphate group must be removed by phosphatases
The concentration of cAMP in a cell is determined by the relative rates of synthesis (adenylate cyclase) and breakdown (phosphodiesterase)
Caffeine, a stimulant found in coffee and other beverages, inhibit phosphodiesterase, causing levels of cAMP to rise  increase heart rate 心跳速率增加, wakefulness 不能入睡, and heightened alertness 警覺性增加
phosphodiesterase (PDE)
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44. cGMP second messenger system
cGMP is a second messenger catalyzed by an enzyme-linked receptor, guanylate cyclase
Guanylate cyclase is more commonly associated with G proteins, in which case the cGMP second messenger system is similar to cAMP but activates protein kinase G, also called cGMP-dependent protein kinase
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45. Phosphatidylinositol second messenger system
Figure 5.17 The phosphatidylinositol second messenger system.
The messenger binds to its receptor, activating a G protein
The G protein releases the a subunit, which binds to and activates the enzyme phospholipase C
Phospholipase C catalyzes the conversion of a membrane phospholipid called phosphatidylinositol 4,5-biphosphate (PIP2) to DAG and IP3, each of which functions as a second messenger
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
a DAG remains in the membrane and activates the enzyme protein kinase C, a which catalyzes the phosphorylation of a protein  a bringing about a response in the cell
b At the same time, IP3 moves into the cytosol  b triggers the release of calcium from the endoplasmic reticulum  b acts on proteins to stimulate contraction or secretion; or c acts as a second messenger by binding to calmodulin, activating a protein kinase that phosphorylates a protein that produces a response in the cell P

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47. Signal amplification in the cAMP second messenger system
The ability of small changes in the concentration of a chemical messenger to elicit marked responses in target cells, a phenomenon known as signal amplification
The net result in Figure 5.18 is that a large number of end- product molecules can be regulated in response to the binding of a single ligand molecule to its receptor
Cascade, a series of sequential steps that progressively increase in magnitude  is common in chemical messenger systems and account for much of the signal amplification that occurs
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.18 Signal amplification, in this case by the second messenger cAMP. P

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49. V. Long Distance Communication via the nervous and endocrine systems
The body has two organ systems specialized for long-distance communication: the nervous system 神經系統 and the endocrine system 內分泌系統
The endocrine system communicates through chemicals called hormones, which travel via the bloodstream to virtually all cells in the body
Hormones generally communicate by altering protein synthesis or activating G proteins, processes that are considerably slower than electrical and chemical signal used by the nervous system P

50. Signal Transmission in Neurons
The nervous system consists of neurons 神經細胞 and supporting cells 支撐性細胞 called glial cells 膠細胞
Neurons are capable of communicating long distance, first by transmitting electrical signals along the length of the cell, and then by transmitting chemical signals through the release of a neurotransmitter at a synapse
Signal transmitted by the nervous system travel quickly and are generally of short duration, making the system ideal for controlling movements and monitoring the world around us
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.19 Signal transmission in neuron. Neurons transmit both electrical signals within the cell and chemical signals between cells.
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