Chapter 8 An Introduction to Metabolism Guided Study

Transcription

1 Chapter 8 An Intrductin t Metablism Guided Study Cncept 8.1 An rganism s metablism transfrms matter and energy, subject t the laws f thermdynamics. The sum ttal f an rganism s chemical reactins is called. Metablism is an emergent prperty f life that arises frm interactins between mlecules within the rderly envirnment f the cell. The chemistry f life is rganized int metablic pathways. A metablic pathway begins with a specific mlecule, which is then altered in a series f defined steps t frm a specific prduct. A specific catalyzes each step f the pathway. pathways release energy by breaking dwn cmplex mlecules t simpler cmpunds. A majr pathway f catablism is cellular respiratin, in which the sugar glucse is brken dwn in the presence f xygen t carbn dixide and water. The energy released by catablic pathways becmes available t d the wrk f the cell, such as ciliary beating r membrane transprt. pathways, als called bisynthetic pathways, cnsume energy t build cmplicated mlecules frm simpler cmpunds. The synthesis f amin acids frm simpler mlecules and the synthesis f a prtein frm amin acids are bth examples f anablism. Energy released frm the dwnhill reactins f catablic pathways can be stred and then used t drive the uphill reactins f anablic pathways. Energy is fundamental t all metablic prcesses, and therefre an understanding f energy is key t understanding hw the living cell wrks. is the study f hw energy flws thrugh living rganisms. Organisms transfrm energy. is the capacity t cause change. In everyday life, sme frms f energy can be used t d wrk that is, t mve matter against ppsing frces, such as gravity and frictin. Energy exists in varius frms, and cells transfrm energy frm ne type t anther. energy is the energy assciated with the relative mtin f bjects. Objects in mtin can perfrm wrk by imparting mtin t ther matter. Thermal energy is kinetic energy assciated with the randm mvement f atms r mlecules. Heat is the transfer f thermal energy frm ne bdy f matter t anther. The energy f light can be harnessed t pwer phtsynthesis in green plants. energy is the energy that matter pssesses because f its lcatin r structure. 8-1

2 Water behind a dam pssesses energy because f its altitude abve sea level. Mlecules pssess energy because f the arrangement f electrns in the bnds between their atms. energy is a term used by bilgists t refer t the ptential energy available fr release in a chemical reactin. During a catablic reactin, sme bnds are brken and thers are frmed, releasing energy and prducing lwer-energy breakdwn prducts. Energy can be frm ne frm t anther. The energy transfrmatins f life are subject t tw laws f thermdynamics. is the study f energy transfrmatins that ccur in a cllectin f matter. In this field, the term system refers t the matter under study, and the surrundings include the rest f the universe everything utside the system. An system, apprximated by liquid in a therms, is unable t exchange either energy r matter with its surrundings. In an system, energy and matter can be transferred between the system and its surrundings. Organisms are pen systems: They absrb energy light r chemical energy in the frm f rganic mlecules and release heat and metablic waste prducts, such as urea r CO 2, t their surrundings. Tw laws f thermdynamics gvern energy transfrmatins in rganisms and all ther cllectins f matter. The first law f thermdynamics states that the energy f the universe is cnstant: Energy can be transferred and transfrmed, but it be created r destryed. The first law is als knwn as the principle f cnservatin f energy. Plants d nt prduce energy; they transfrm light energy t chemical energy. During every transfer r transfrmatin f energy, sme energy is cnverted t heat, which is the energy assciated with the randm mvement f atms and mlecules. A system can use heat t d wrk nly when there is a temperature difference that results in heat flwing frm a warmer lcatin t a cler ne. If temperature is unifrm, as in a living cell, heat can be used nly t warm the rganism. Energy transfers and transfrmatins make the universe mre disrdered due t the lss f usable energy. is a measure f disrder r randmness: The mre randm a cllectin f matter, the greater its entrpy. The secnd law f thermdynamics states: Every energy transfer r transfrmatin the entrpy f the universe. Althugh rder can increase lcally, there is an unstppable trend tward randmizatin f the universe. Much f the increased entrpy f the universe takes the frm f increasing heat, which is the energy f randm mlecular mtin. prcesses can ccur withut an input f energy, althugh they need nt ccur quickly. Sme spntaneus prcesses, such as an explsin, are instantaneus. Sme, such as the rusting f an ld car, are very slw. 8-2

3 A spntaneus prcess is ne that is energetically favrable. A prcess that cannt ccur n its wn is said t be nnspntaneus: it will happen nly if energy is added t the system. Water flws dwnhill spntaneusly but mves uphill nly with an input f energy, such as when a machine pumps the water against gravity. Here is anther way t state the secnd law f thermdynamics: Fr a prcess t ccur spntaneusly, it must increase the entrpy f the universe. Living systems increase the entrpy f their surrundings, even thugh they create rdered structures frm less rdered starting materials. Fr example, amin acids are rdered int plypeptide chains. This increase in rganizatin des nt vilate the secnd law f thermdynamics. Organisms are islands f lw entrpy in an increasingly randm universe. Cncept 8.2 The free-energy change f a reactin tells us whether r nt the reactin ccurs spntaneusly. Hw can we determine which reactins ccur spntaneusly and which nes require an input f energy? The cncept f free energy (symblized by the letter G) is useful fr measuring the spntaneity f a system. energy is the prtin f a system s energy that can perfrm wrk when temperature and pressure are unifrm thrughut the system, as in a living cell. The change in free energy, G, can be calculated fr any specific chemical reactin by applying the fllwing equatin: G = T In this equatin, H symblizes the change in the system s (in bilgical systems, equivalent t ttal energy); S is the change in the system s ; and T is the temperature in Kelvin (K) units (K = C + 273). Fr a prcess t ccur spntaneusly, the system must give up enthalpy (H must decrease), give up rder (T S must increase), r bth. G must have a (psitive/negative?) value ( G < 0) in rder fr a prcess t be spntaneus. In ther wrds, every spntaneus prcess decreases the system s free energy, and prcesses that have psitive r zer G are never spntaneus. Knwing the value f G gives bilgists the pwer t predict which kinds f change can happen withut help. Such spntaneus changes can be harnessed t perfrm wrk. In any spntaneus prcess, the free energy f a system decreases ( G is negative). Anther term fr a state f maximum stability is equilibrium. In a chemical reactin at equilibrium, the rates f frward and backward reactins are equal, and there is n change in the relative cncentratins f prducts r reactants. At equilibrium, G = 0, and the system can d n wrk. The cell is dead. Fr a cell t wrk, G 0. (Metablic disequilibrium) Chemical reactins can be classified as either exergnic r endergnic. An reactin prceeds with a net release f free energy; G is negative. The magnitude f G fr an exergnic reactin is the maximum amunt f wrk the reactin can perfrm. 8-3

4 The greater the (decrease/increase?) in free energy, the greater the amunt f wrk that can be dne. Fr the verall reactin f cellular respiratin, C 6H 12O 6 + 6O 2 6CO 2 + 6H 2O, G = 686 kcal/ml. Fr each mle (180 g) f glucse brken dwn by respiratin under standard cnditins (1 M f each reactant and prduct, 25 C, ph 7), 686 kcal f energy are made available t d wrk in the cell. The prducts have 686 kcal less free energy per mle than the reactants. An reactin is ne that absrbs free energy frm its surrundings. Endergnic reactins stre energy in mlecules; G is (psitive/negative?). Endergnic reactins are nnspntaneus, and the magnitude f G is the quantity f energy required t drive the reactin. Reactins in an islated system eventually reach equilibrium and can d n wrk. A cell that has reached metablic equilibrium has a G = 0 and is dead! Metablic disequilibrium is ne f the defining features f life. Cells maintain disequilibrium because they are pen systems. The cnstant flw f materials int and ut f the cell keeps metablic pathways frm ever reaching equilibrium. A cell cntinues t d wrk thrughut its life. As lng as cells have a steady supply f glucse r ther fuels and xygen and can expel waste prducts t the surrundings, their metablic pathways never reach equilibrium and can cntinue t d the wrk f life. Sunlight prvides a daily surce f free energy fr phtsynthetic rganisms. Nn-phtsynthetic rganisms depend n a transfer f free energy frm phtsynthetic rganisms in the frm f rganic mlecules. Cncept 8.3 ATP pwers cellular wrk by cupling exergnic reactins t endergnic reactins. A cell des three main kinds f wrk: 1. wrk, pushing endergnic reactins such as the synthesis f plymers frm mnmers; 2. wrk, pumping substances acrss membranes against the directin f spntaneus mvement; 3. wrk, such as the beating f cilia, cntractin f muscle cells, and mvement f chrmsmes during cellular reprductin; Cells manage their energy resurces t d this wrk by, using an exergnic prcess t drive an endergnic ne. ATP mediates mst energy cupling in cells. ATP ( ) is a nucletide triphsphate cnsisting f the sugar ribse, the nitrgenus base adenine, and a chain f three phsphate grups. In mst cases, ATP acts as the immediate surce f energy that pwers cellular wrk. The bnds between the phsphate grups n ATP can be brken by hydrlysis. ATP + H 2O ADP + P i Under standard cnditins, G = 7.3 kcal/ml (30.5 kj/ml). Why des the hydrlysis f ATP yield s much energy? Each f the three phsphate grups has a negative charge. 8-4

5 These three like charges are crwded tgether, and their mutual repulsin cntributes t the instability f this regin f the ATP mlecule. In the cell, the energy frm the hydrlysis f ATP is directly cupled t endergnic prcesses by the transfer f the phsphate grup t anther mlecule. This recipient mlecule with a phsphate grup cvalently bnded t it is called a phsphrylated intermediate. It is mre reactive (less stable) than the riginal unphsphrylated mlecule. Mechanical, transprt, and chemical wrk in the cell are nearly always pwered by the f ATP. ATP is a renewable resurce. Althugh rganisms use ATP cntinuusly, ATP is a renewable resurce that can be regenerated by the additin f a phsphate grup t ADP. Catablic (exergnic) pathways, especially cellular respiratin, prvide the energy fr the endergnic regeneratin f ATP. Additinally, plants als use light energy t prduce ATP. The chemical ptential energy temprarily stred in ATP drives mst cellular wrk. Cncept 8.4 Enzymes speed up metablic reactins by lwering energy barriers. An enzyme is a macrmlecule that acts as a, a chemical agent that speeds up the rate f a reactin withut being cnsumed by the reactin. Every chemical reactin invlves bnd and bnd frming. The initial investment f energy fr starting a reactin is the free energy f activatin, r energy (E A). Activatin energy is the amunt f energy necessary t push the reactants ver an energy barrier s that the dwnhill part f the reactin can begin. Activatin energy is ften supplied in the frm f thermal energy that the reactant mlecules absrb frm the surrundings. The absrptin f thermal energy accelerates the reactant mlecules, which then cllide mre ften with mre frce. It als agitates the atms within the mlecules, making the breakage f bnds mre likely. When the mlecules have absrbed enugh energy fr the bnds t break, the reactants are in an unstable cnditin called the transitin state. Hwever, there is nt enugh energy at the temperatures typical f the cell fr the vast majrity f rganic mlecules t make it ver the hump f activatin energy. Hw are the barriers fr selected reactins surmunted t allw cells t carry ut the prcesses f life? Heat wuld speed up all reactins, nt just thse that are needed. Heat als denatures prteins and kills cells. Enzymes speed reactins by (lwering/increasing?) E A. The transitin state can then be reached even at mderate temperatures. Because enzymes are s selective, they determine which chemical prcesses will ccur at any time. 8-5

6 Enzymes are substrate specific. The reactant that an enzyme acts n is the. The enzyme binds t a substrate, r substrates, frming an - cmplex. While the enzyme and substrate are bund, the catalytic actin f the enzyme cnverts the substrate t the prduct r prducts. The reactin catalyzed by each enzyme is very specific. The site f an enzyme is typically a pcket r grve n the surface f the prtein where catalysis ccurs. The specificity f an enzyme is due t the fit between the and the. As the substrate enters the active site, interactins between the chemical grups n the substrate and thse n the side chains f the amin acids that frm the active site cause the enzyme t change shape slightly. This change leads t an fit that brings the chemical grups f the active site int psitin t catalyze the reactin. The active site is an enzyme s catalytic center. The substrate is cnverted t prduct within the active site, the prduct then leaves the active site. A single enzyme mlecule can catalyze thusands f reactins a secnd. Enzymes are (affected/ nt affected?) by the reactin and are reusable. Enzymes use a variety f mechanisms t lwer the activatin energy and speed up a reactin. In reactins invlving mre than ne reactant, the active site brings substrates tgether in the crrect rientatin fr the reactin t prceed. Enzymes may briefly bind cvalently t substrates. Subsequent steps f the reactin restre the side chains f amin acids within the active site t their riginal state. The rate at which a specific number f enzymes cnvert substrates t prducts depends in part n substrate cncentratins. At lw substrate cncentratins, an increase in substrate cncentratin speeds binding t available active sites. There is a limit t hw fast a reactin can ccur, hwever. At high substrate cncentratins, the active sites n all enzymes are engaged. The enzyme is saturated, and the rate f the reactin is determined by the speed at which the active site can cnvert substrate t prduct. The nly way t increase prductivity at this pint is t add mre enzyme mlecules. A cell s physical and chemical envirnment affects enzyme activity. The activity f an enzyme is affected by general envirnmental cnditins, such as and. Each enzyme wrks best at certain ptimal cnditins, which favr the mst active cnfrmatin fr the enzyme mlecule. Temperature has a majr impact n reactin rate. As temperature increases, cllisins between substrates and active sites ccur (mre/less?) frequently as mlecules mve mre rapidly. As temperature increases further, thermal agitatin begins t disrupt the weak bnds that stabilize the prtein s active cnfrmatin, and the prtein denatures. 8-6

7 Each enzyme has an ptimal temperature that allws the greatest number f mlecular cllisins and the fastest cnversin f the reactants t prduct mlecules. Mst human enzymes have ptimal temperatures f abut C. The thermphilic bacteria that live in ht springs cntain enzymes with ptimal temperatures f 70 C r higher. Each enzyme als has an ptimal ph. Maintenance f the active cnfrmatin f the enzyme requires a particular ph. This ptimal ph falls between 6 8 fr mst enzymes. Hwever, digestive enzymes in the stmach are designed t wrk best at ph 2, whereas thse in the intestine have an ptimal ph f 8. Many enzymes require nnprtein helpers, called cfactrs, fr catalytic activity. Cfactrs bind permanently r reversibly t the enzyme. Sme inrganic cfactrs are zinc, irn, and cpper in inic frm. Organic cfactrs are called. Mst vitamins are cenzymes r the raw materials frm which cenzymes are made. Binding by inhibitrs prevents enzymes frm catalyzing reactins. Certain chemicals selectively inhibit the actin f specific enzymes. If inhibitrs attach t the enzyme by cvalent bnds, inhibitin may be irreversible. If inhibitrs bind by weak bnds, inhibitin may be reversible. Sme irreversible inhibitrs resemble the substrate and cmpete fr binding t the active site. These mlecules are called inhibitrs. inhibitrs impede enzymatic reactins by binding t anther part f the mlecule. Binding by the inhibitr causes the enzyme t change shape, rendering the active site less effective at catalyzing the reactin. Txins and pisns are ften irreversible enzyme inhibitrs. Examples: Sarin, the nerve gas that was released by terrrists in the Tky subway in 1995, binds cvalently t the R grup n the amin acid serine. Serine is fund in the active site f acetylchlinesterase, an imprtant nervus system enzyme. DDT acts as a pesticide by inhibiting key enzymes in the nervus system f insects. Many antibitics are inhibitrs f specific enzymes in bacteria. Ex. Penicillin blcks the active site f an enzyme that many bacteria use t make their cell walls. Cncept 8.5 Regulatin f enzyme activity helps cntrl metablism. Metablic cntrl ften depends n allsteric regulatin. Many mlecules that naturally regulate enzyme activity behave like reversible nncmpetitive inhibitrs. In allsteric regulatin, a prtein s functin at ne site is affected by the binding f a regulatry mlecule t a separate site resulting in either inhibitin r stimulatin f an enzyme s activity. Mst allsterically regulated enzymes are cnstructed f tw r mre plypeptide chains. The cmplex scillates between tw shapes, ne catalytically active and the ther inactive. 8-7

8 The binding f an (activatr/inhibitr?) stabilizes the cnfrmatin that has functinal active sites, whereas the binding f an (activatr/inhibitr?) stabilizes the inactive frm f the enzyme. In enzymes with multiple catalytic subunits, binding by a substrate mlecule t ne active site in a multisubunit enzyme triggers a shape change in all the subunits. This mechanism, called cperativity, amplifies the respnse f enzymes t substrates, priming the enzyme t accept additinal substrates. Cperativity is cnsidered t be allsteric regulatin because binding f the substrate t ne active site affects catalysis in a different active site. The vertebrate xygen-transprt prtein hemglbin is a classic example f cperativity. Hemglbin is made up f fur subunits, each with an xygen-binding site. The binding f an xygen mlecule t each binding site increases the affinity fr xygen f the remaining binding sites. Under cnditins f lw xygen, as in xygen-deprived tissues, hemglbin is less likely t bind xygen and releases it where it is needed. A cmmn methd f metablic cntrl is inhibitin in which an early step in a metablic pathway is switched ff by inhibitry binding f the pathway s final prduct t an enzyme acting early in the pathway. Feedback inhibitin prevents a cell frm wasting chemical resurces by synthesizing mre prduct than is needed. 8-8