國防醫學院 生物及解剖學科

陳 正 繹

BioA-Ch7-8-Memb & Meta 2017

Ch 7 Membrane Structure and Function (Ch 8 Cell Membranes)

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7.0 Overview: Life at the Edge * The plasma membrane is the boundary that separates the living cell

from its surroundings

* The plasma membrane exhibits selective permeability選擇性透過, allowing some substances to cross it more easily than others

How do cell membrane proteins help regulate chemical traffic?

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Video: Structure of the Cell Membrane

How do cell membrane proteins help regulate chemical traffic?

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Figure 7.1a

K+ channel

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Key Concepts

7.1 Cellular membranes are fluid mosaics of lipids and proteins

7.2 Membrane structure results in selective permeability

7.3 Passive transport is diffusion of a substance across a membrane with no energy

7.4 Active transport uses energy to move solutes against their gradients

7.5 Bulk transport across the plasma membrane occurs by exocytosis and endocytosis

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7.1: Cellular membranes are fluid mosaics of lipids and proteins

* Phospholipids 磷脂質are the

most abundant lipid in the plasma membrane

* Phospholipids are amphipathic molecules兩性分子, containing hydrophobic 疏水性and hydrophilic 親水性regions

* A phospholipid bilayer can exist as a stable boundary between two aqueous compartments

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*The fluid mosaic model 液體鑲嵌模型states that a membrane is a fluid structure with a “mosaic” of various proteins embedded in it

*Proteins are not randomly distributed in the membrane

Updated model of an animal cells plasma membrane

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Do membrane protein move?

A. The Fluidity of Membranes • Phospholipids in the plasma membrane can move within the bilayer

• Most of the lipids, and some proteins, drift laterally

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*Rarely does a molecule flip-flop 翻跟斗transversely across the membrane

Fig The movement of phospholipids

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* As temperatures cool, membranes switch from a fluid state to a solid state * The temperature at which a membrane solidifies depends on the types of

lipids * Membranes rich in unsaturated fatty acids 不飽和脂肪酸are more fluid

than those rich in saturated fatty acids

* Membranes must be fluid to work properly; they are usually about as fluid as salad oil

* The steroid cholesterol膽固醇as “fluidity buffer” has different effects on membrane fluidity at different temperatures

* At warm temperatures (such as 37°C), cholesterol restrains movement of phospholipids

* At cool temperatures, it maintains fluidity by preventing tight packing

Fig The movement of phospholipids

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B. Evolution of Differences in Membrane Lipid Composition

Variations in lipid composition of cell membranes of many species appear to be adaptations to specific environmental conditions. Ex. Fishes in extreme cold

Ability to change the lipid compositions in response to temperature changes has evolved in organisms that live where temperatures vary. Ex.

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C. Membrane Proteins and Their Functions A membrane is a collage of different proteins,

often grouped together as “mosaic”, embedded in the fluid matrix of the lipid bilayer

Proteins determine most of the membrane’s specific functions

Peripheral proteins 週邊蛋白are bound to the surface of the membrane

Integral proteins 嵌入蛋白penetrate the hydrophobic core

Integral proteins that span the membrane are called transmembrane proteins 穿膜蛋白

The hydrophobic regions 疏水區of an integral protein consist of one or more stretches of nonpolar amino acids, often coiled into alpha helices

Fig The structure of transmembrane protein

mosaic

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Six major functions of membrane proteins

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D. The Role of Membrane Carbohydrates in Cell-Cell Recognition

• Cells recognize each other by binding to molecules, often

containing carbohydrates, on the extracellular surface of the

plasma membrane

• Membrane carbohydrates may be covalently bonded to lipids

(forming glycolipids醣脂) or more commonly to proteins (forming glycoproteins醣蛋白)

• Carbohydrates on the external side of the plasma membrane

vary among species, individuals, and even cell types in an

individual

15 Fig Blocking HIV entry into cells as a treatment for HIV infections

16 Fig Synthesis of membrane components and their orientation in the membrane

E. Synthesis and Sidedness of Membranes *Membranes have distinct inside and outside faces

*The asymmetrical 不對稱distribution of proteins, lipids, and associated carbohydrates in the plasma membrane is determined when the membrane is built by the ER and Golgi apparatus

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7.2: Membrane structure results in selective permeability * A cell must exchange materials with its surroundings, a

process controlled by the plasma membrane

* Plasma membranes are selectively permeable, regulating the cell’s molecular traffic

A. The Permeability of the Lipid Bilayer * Hydrophobic疏水性 (nonpolar非極性) molecules, such as

hydrocarbons, can dissolve in the lipid bilayer and pass through the membrane rapidly

* Hydrophilic親水性molecules including ions and polar極性molecules, do not cross the membrane easily

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B. Transport Proteins * Transport proteins輸導蛋白 allow passage of hydrophilic substances

across the membrane

* Some transport proteins, called channel proteins通道蛋白, have a hydrophilic channel that certain molecules or ions can use as a tunnel

* Channel proteins called aquaporin水孔蛋白 facilitate the passage of water

* Other transport proteins, called carrier proteins攜帶蛋白, bind to molecules and change shape to shuttle them across the membrane

* A transport protein is specific for the substance it moves

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Video: Water Movement Through an Aquaporin

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* Diffusion擴散 is the tendency for molecules to spread out evenly into the available space

* Although each molecule moves randomly, diffusion of a population of molecules may be directional

* At dynamic equilibrium動態平衡, as many molecules cross the membrane in one direction as in the other

7.3: Passive transport is diffusion of a substance across a

membrane with no energy investment

Fig The diffusion of solutes across a synthetic membrane

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* Substances diffuse down their concentration gradient濃度梯度, the region along which the density of a chemical substance increases or decreases

* No work must be done to move substances down the concentration gradient

* The diffusion of a substance across a biological membrane is passive transport被動運輸 because no energy is expended by the cell to make it happen

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A. Effects of Osmosis on Water Balance * Osmosis滲透 is the diffusion of water across a selectively permeable

membrane

*Water diffuses across a membrane from the region of lower solute concentration to the region of higher solute concentration until the solute concentration is equal on both sides

Fig Osmosis

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1. Water Balance of Cells Without Walls

* Tonicity張力 is the ability of a surrounding solution to cause a cell to gain or lose water

* Isotonic 等張solution: solute concentration is the same as that inside the cell; no net water movement across the plasma membrane

* Hypertonic 高張solution: solute concentration is greater than that inside the cell; cell loses water

* Hypotonic 低張solution: solute concentration is less than that inside the cell; cell gains water

Fig The water balance of living cells

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* Hypertonic or hypotonic environments create osmotic problems for organisms

* Osmoregulation滲透調節, the control of solute concentrations and water balance, is a necessary adaptation for life in such environments

* The protista Paramecium草履蟲, which is hypertonic to its pond water environment, has a contractile vacuole that acts as a pump

Fig The contractile vacuole伸縮泡of Paramecium caudatum.

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2. Water Balance of Cells with Cell Walls

* Cell walls help maintain water balance

* A plant cell in a hypotonic solution swells until the wall opposes uptake; the cell is now turgid膨脹 (firm)

* If a plant cell and its surroundings are isotonic, there is no net movement of water into the cell; the cell becomes flaccid軟弱的(limp鬆弛的)

* In a hypertonic environment, plant cells lose water; eventually, the membrane pulls away from the wall, a usually lethal effect called plasmolysis(原生質離)

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Video: Plasmolysis

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B. Facilitated Diffusion: Passive Transport Aided by Proteins * In facilitated diffusion促進性擴散, transport proteins speed the passive

movement of molecules across the plasma membrane

* Transport proteins include channel proteins and carrier proteins

* Channel proteins provide corridors that allow a specific molecule or ion to cross the membrane

* Channel proteins include

-Aquaporins水通道蛋白, for facilitated diffusion of water

-Ion channels 離子通道facilitate the diffusion of ions

-Some ion channels, called gated channels閘門通道that open or close in response to a stimulus

Fig Two types of transport protein that carry out facilitated diffusion

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* Carrier proteins undergo a subtle change in shape that translocates the solute-binding site across the membrane

* Some diseases are caused by malfunctions in specific transport systems, for example the kidney disease cystinuria胱氨酸尿症

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7.4: Active transport uses energy to move solutes

against their gradients

* Facilitated diffusion is still passive because the solute moves down its concentration gradient, and the transport requires no energy

* Some transport proteins, however, can move solutes against their concentration gradients

A. The Need for Energy in Active Transport * Active transport 主動運輸moves substances against their concentration

gradient

* Active transport requires energy, usually in the form of ATP

* Active transport is performed by specific proteins embedded in the membranes

* Active transport allows cells to maintain concentration gradients that differ from their surroundings

* The sodium-potassium pump 鈉鉀泵is one type of active transport system

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The sodium-potassium pump: a

specific case of active transport

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Animation: Active Transport

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Review positive and active transport

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B. How Ion Pumps Maintain Membrane Potential * Membrane potential膜電位 is the voltage difference across a membrane * Voltage is created by differences in the distribution of positive and negative ions

across a membrane * Two combined forces, collectively called the electrochemical gradient電化梯度, drive

the diffusion of ions across a membrane * A chemical force (the ion’s concentration gradient) * An electrical force (the effect of the membrane potential on the ion’s movement) * An electrogenic pump生電泵is a transport protein that generates voltage across a

membrane * The sodium-potassium pump is the major electrogenic pump of animal cells * The main electrogenic pump of plants, fungi, and bacteria is a proton pump質子泵 * Electrogenic pumps help store energy that can be used for cellular work

Fig A proton pump

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C. Cotransport: Coupled Transport by a Membrane Protein * Cotransport 同向運輸occurs when active transport of a solute indirectly

drives transport of other solutes

* Plants commonly use the gradient of hydrogen ions generated by proton pumps to drive active transport of nutrients into the cell

Cotransport: active transport driven by a gradient concentration.

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BioFlix: Membrane Transport

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7.5: Bulk transport across the plasma membrane occurs by exocytosis and endocytosis

* Small molecules and water enter or leave

the cell through the lipid bilayer or via transport proteins

* Large molecules, such as polysaccharides and proteins, cross the membrane in bulk via vesicles囊泡

* Bulk transport requires energy

A. Exocytosis * In exocytosis胞吐, transport vesicles

migrate to the membrane, fuse with it, and release their contents outside the cell

* Many secretory cells use exocytosis to export their products

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B. Endocytosis In endocytosis胞吞, the cell takes in macromolecules by forming

vesicles from the plasma membrane

Endocytosis is a reversal of exocytosis, involving different proteins

There are three types of endocytosis

-Phagocytosis (“cellular eating”) 胞噬

-Pinocytosis (“cellular drinking”) 胞飲

-Receptor-mediated endocytosis受體媒介的胞飲作用

In phagocytosis a cell engulfs a particle in a vacuole

The vacuole fuses with a lysosome溶素體 to digest the particle

In pinocytosis, molecules are taken up when extracellular fluid is “gulped” into tiny vesicles

In receptor-mediated endocytosis, binding of ligands配體 to receptors 受體triggers vesicle formation

A ligand is any molecule that binds specifically to a receptor site of another molecule.

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Ch 8 An Introduction to Metabolism

(Ch 6 Energy and Life)

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8.0 Overview: The Energy of Life * The living cell is a miniature chemical factory where thousands of reactions

occur

* The cell extracts energy and applies energy to perform work

* Some organisms even convert energy to light, as in bioluminescence生物光

Fig What causes these breaking waves to glow?

Key Concepts

8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics

8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously

8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions

8.4: Enzymes speed up metabolic reactions by lowering energy barriers

8.5: Regulation of enzyme activity helps control metabolism

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8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics熱動力學、熱力學

* Metabolism代謝 is the totality of an organism’s chemical reactions

* Metabolism is an emergent property of life that arises from interactions between molecules within the cell

A. Organization of the Chemistry of Life into Metabolic Pathways

* A metabolic pathway代謝路徑begins with a specific molecule and ends with a product

* Each step is catalyzed催化 by a specific enzyme酶;酵素

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* Catabolic pathways異化路徑 release energy by breaking down complex molecules into simpler compounds

* Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism異化作用

* Anabolic pathways同化路徑 consume energy to build complex molecules from simpler ones

* The synthesis of protein from amino acids is an example of anabolism異化作用

* Bioenergetics生物能量學 is the study of how organisms manage their energy resources

B. Forms of Energy * Energy is the capacity to cause change

* Energy exists in various forms, some of which can perform work

* Kinetic energy動能 is energy associated with motion

* Heat (thermal energy)熱能 is kinetic energy associated with random movement of atoms or molecules

* Potential energy位能 is energy that matter possesses because of its location or structure

* Chemical energy 化學能is potential energy available for release in a chemical reaction

* Energy can be converted from one form to another

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Transformations between potential and kinetic energy

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C. The Laws of Energy Transformation * Thermodynamics熱力學is the study of energy transformations

* A isolated system封閉系統, such as that approximated by liquid in a thermos, is isolated from its surroundings

* In an open system開放系統, energy and matter can be transferred between the system and its surroundings

* Organisms are open systems

1. The First Law of Thermodynamics熱力學第一定律

* According to the first law of thermodynamics, the energy of the universe is constant

* Energy can be transferred and transformed, but it cannot be created or destroyed

* The first law is also called the principle of conservation of energy能量守恆

2. The Second Law of Thermodynamics熱力學第二定律

* During every energy transfer or transformation, some energy is unusable, and is often lost as heat

* According to the second law of thermodynamics

* Every energy transfer or transformation increases the entropy熵 (disorder亂度) of the universe

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The two laws of thermodynamics

*Living cells unavoidably convert organized forms of energy to heat

*Spontaneous processes自發變化occur without energy input; they can happen quickly or slowly

*For a process to occur without energy input, it must increase the entropy of the universe

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3. Biological Order and Disorder *Cells create ordered structures from less ordered materials

*Organisms also replace ordered forms of matter and energy with less ordered forms

*Energy flows into an ecosystem in the form of light and exits in the form of heat

*The evolution of more complex organisms does not violate不違背the second law of thermodynamics

*Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases

Fig Order as a characteristic of life

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*Biologists want to know which reactions occur spontaneously and which require input of energy

* To do so, they need to determine energy changes that occur in chemical reactions

A. Free-Energy Change, G * A living system’s free energy自由能is energy that can do work when

temperature and pressure are uniform, as in a living cell * The change in free energy (∆G) during a process is related to the change in

enthalpy焓, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T)

∆G = ∆H – T∆S * Only processes with a negative ∆G are spontaneous * Spontaneous processes can be harnessed to perform work

B. Free Energy, Stability, and Equilibrium * Free energy is a measure of a system’s instability, its tendency to change to a

more stable state * During a spontaneous change, free energy decreases and the stability of a

system increases * Equilibrium is a state of maximum stability * A process is spontaneous and can perform work only when it is moving

toward equilibrium

8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously

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The relationship of free energy to stability, work capacity, and spontaneous change

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C. Free Energy and Metabolism * The concept of free energy can be

applied to the chemistry of life’s processes

1. Exergonic and Endergonic Reactions in Metabolism

* An exergonic reaction釋能的proceeds with a net release of free energy and is spontaneous

* An endergonic reaction吸能的absorbs free energy from its surroundings and is nonspontaneous

Fig Free energy changes (∆G)in exergonic and endergonic reactions

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2. Equilibrium and Metabolism

*Reactions in a closed system封閉系統 eventually reach equilibrium and then do no work

*Cells are not in equilibrium; they are open systems experiencing a constant flow of materials

*A defining feature of life is that metabolism is never at equilibrium

*A catabolic pathway in a cell releases free energy in a series of reactions

*Closed and open hydroelectric systems can serve as analogies類似物

Fig Equilibrium and work in isolated and open systems

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8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions

* A cell does three main kinds of work

* Chemical, Transport, Mechanical

* To do work, cells manage energy resources by energy coupling能量耦合, the use of an exergonic process to drive an endergonic one

* Most energy coupling in cells is mediated by ATP

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* ATP (adenosine triphosphate) is the

cell’s energy shuttle

* ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups

* The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis

* Energy is released from ATP when the terminal phosphate bond is broken

* This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves

Fig The structure and hydrolysis of adenosine triphosphate(ATP)

A. The Structure and Hydrolysis of ATP

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B. How the Hydrolysis of ATP Performs Work

* The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP

* In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction

* Overall, the coupled reactions are exergonic

How ATP drives chemical work: Energy coupling using ATP hydrolysis

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ATP drives endergonic reactions by phosphorylation磷酸化, transferring a phosphate group to some other molecule, such as a reactant

The recipient molecule is now called a phosphorylated intermediate 磷酸化的中間產物

Transport and mechanical work in the cell are also powered by ATP hydrolysis

ATP hydrolysis leads to a change in protein shape and binding ability

Fig How ATP drives transport and mechanical work

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C. The Regeneration of ATP

* ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)

* The energy to phosphorylate ADP comes from catabolic reactions in the cell

* The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways.

Fig The ATP cycle

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8.4: Enzymes speed up metabolic reactions by

lowering energy barriers

* A catalyst催化劑 is a chemical agent that speeds up a reaction without being consumed by the reaction

* An enzyme酶 is a catalytic protein

* Hydrolysis of sucrose by the enzyme sucrase蔗糖酶 is an example of an enzyme-catalyzed reaction

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Every chemical reaction between molecules involves bond breaking and bond forming

Fig Energy profile of an exergonic reaction

A. The Activation Energy Barrier

The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA)活化能

Activation energy is often supplied in the form of thermal energy that the reactant molecules absorb from their surroundings

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* Enzymes catalyze reactions by lowering the EA barrier * Enzymes do not affect the change in free energy (∆G); instead, they hasten加速reactions that would occur eventually

Fig The effect of an enzyme on activation

B. How Enzymes Speed Up Reactions

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C. Substrate Specificity of Enzymes * The reactant that an enzyme acts on is called the enzyme’s substrate受質 * The enzyme binds to its substrate, forming an enzyme-substrate complex酶受質複合體

* The reaction catalyzed by each enzyme is very specific * The active site活化位置 is the region on the enzyme where the substrate

binds * Induced fit誘導適合 of a substrate brings chemical groups of the active site

into positions that enhance their ability to catalyze the reaction

Fig Induced fit between enzyme and its substrate

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D. Catalysis催化反應 in the Enzyme’s Active Site *In an enzymatic reaction, the substrate binds to the active site of the enzyme *In step3: The active site can lower an EA barrier by following

Figure 8.15 The active site and catalytic cycle of an enzyme

a.Orienting substrates correctly

b.Straining substrate bonds

c.Providing a favorable microenvironment

d.Covalently bonding to the substrate

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E. Effects of Local Conditions on Enzyme Activity *An enzyme’s activity can be affected by

Fig Environmental factors affecting enzyme activity

1. Effects of Temperature and pH

* Each enzyme has an optimal temperature in which it can function

* Each enzyme has an optimal pH in which it can function

* Optimal conditions favor the most active shape for the enzyme molecule

a. General environmental factors, such as temperature and pH.

b. Chemicals that specifically influence the enzyme

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2. Cofactor

*Cofactors輔因子are nonprotein enzyme helpers *Cofactors may be inorganic (such as a metal in ionic form) or organic *An organic cofactor is called a coenzyme輔酶 *Coenzymes include vitamins

3. Enzyme Inhibitors

* Competitive inhibitors競爭性抑制物 bind to the active site of an enzyme, competing with the substrate

* Noncompetitive inhibitors非競爭性抑制物 bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective

* Examples of inhibitors include toxins, poisons, pesticides, and antibiotics

Fig Inhibition of enzyme activity

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F. The Evolution of Enzymes * Enzymes are proteins encoded by genes

* Changes (mutations突變) in genes lead to changes in amino acid composition of an enzyme

* Altered amino acids in enzymes may alter their substrate specificity

* Under new environmental conditions a novel form of an enzyme might be favored

Fig Mimicking evolution of an enzyme with a new function

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* Chemical chaos混亂would result if a cell’s metabolic pathways were not

tightly regulated

* A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes

A, Allosteric Regulation of Enzymes * Allosteric regulation異位調節may either inhibit or stimulate an

enzyme’s activity

* Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site

1. Allosteric Activation and Inhibition

* Most allosterically regulated enzymes are made from polypeptide subunits

* Each enzyme has active and inactive forms

* The binding of an activator stabilizes the active form of the enzyme

* The binding of an inhibitor stabilizes the inactive form of the enzyme

8.5: Regulation of enzyme activity helps control

metabolism

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Allosteric regulation of enzyme activity

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* Cooperativity 協同性is a form of allosteric regulation that can amplify enzyme activity

* One substrate molecule primes an enzyme to act on additional

substrate molecules more readily

* Cooperativity is allosteric because binding by a substrate to one

active site affects catalysis in a different active site

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2. Feedback Inhibition

* In feedback inhibition回饋抑制, the end product of a metabolic pathway shuts down the pathway

Fig Feedback inhibition in isoleucine synthesis

*Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed

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*Structures within the cell help bring order to metabolic pathways

*Some enzymes act as structural components of membranes

*In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria粒線體

B. Specific Localization of Enzymes Within the Cell

Fig Organelles and structural order in metabolism

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The End