Campbell Chapter 8: Introduction to Metabolism PDF

AN  INTRODUCTION  TO   METABOLISM    The  Energy  of  Life   The  living  cell  is  a  miniature  chemical  factory   where  thousands  of  reac8ons  occur   The  cell  extracts  energy  stored  in  sugars  and   oth...

AN  INTRODUCTION  TO   METABOLISM    The  Energy  of  Life   The  living  cell  is  a  miniature  chemical  factory   where  thousands  of  reac8ons  occur   The  cell  extracts  energy  stored  in  sugars  and   other  fuels  and  applies  energy  to  perform   work    An  organism’s  metabolism  transforms  ma>er   and  energy,  subject  to  the  laws  of   thermodynamics   Metabolism  is  the  totality  of  an  organism’s   chemical  reac8ons   Metabolism  is  an  emergent  property  of  life  that   arises  from  orderly  interac8ons  between   molecules      Catabolic  pathways  release  energy  by   breaking  down  complex  molecules  into   simpler  compounds   Cellular  respira8on,  the  breakdown  of  glucose   in  the  presence  of  oxygen,  is  an  example  of  a   pathway  of  catabolism      Anabolic  pathways  consume  energy  to  build   complex  molecules  from  simpler  ones   The  synthesis  of  protein  from  amino  acids  is   an  example  of  anabolism   BioenergeAcs  is  the  study  of  how  energy   flows  through  living  organisms    Forms  of  Energy   Energy  is  the  capacity  to  cause  change   Energy  exists  in  various  forms,  some  of  which   can  perform  work      KineAc  energy  is  energy  associated  with  mo8on   Heat  (thermal  energy)  is  kine8c  energy   associated  with  random  movement  of  atoms   or  molecules   PotenAal  energy  is  energy  that  ma>er  possesses   because  of  its  loca8on  or  structure   Chemical  energy  is  poten8al  energy  available   for  release  in  a  chemical  reac8on     Energy  can  be  converted  from  one  form  to   another   A diver has more potential Diving converts energy on the platform potential energy to than in the water. Figure  8.2   kinetic energy. Climbing up converts the kinetic A diver has less potential energy of muscle movement energy in the water to potential energy. than on the platform. The  Laws  of  Energy  Transforma8on   Thermodynamics  is  the  study  of  energy   transforma8ons   An  isolated  system,  such  as  that  approximated   by  liquid  in  a  thermos,  is  unable  to  exchange   energy  or  ma>er  with  its  surroundings   In  an  open  system,  energy  and  ma>er  can   be  transferred  between  the  system  and  its   surroundings   Organisms  are  open  systems    The  First  Law  of  Thermodynamics   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   conserva8on  of  energy    The  Second  Law  of  Thermodynamics   During  every  energy  transfer  or   transforma8on,  some  energy  is  unusable,  and   is  oMen  lost  as  heat   According  to  the  second  law  of   thermodynamics   – Every  energy  transfer  or  transforma;on  increases   the  entropy  (disorder)  of  the  universe      Living  cells  unavoidably  convert  organized   forms  of  energy  to  heat   Spontaneous  processes  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    Biological  Order  and  Disorder   Cells  create  ordered  structures  from  less   ordered  materials   Organisms  also  replace  ordered  forms  of   ma>er  and  energy  with  less  ordered  forms   Energy  flows  into  an  ecosystem  in  the  form  of   light  and  exits  in  the  form  of  heat      The  evolu8on  of  more  complex  organisms   does  not  violate  the  second  law  of   thermodynamics   Entropy  (disorder)  may  decrease  in  an   organism,  but  the  universe’s  total  entropy   increases    The  free-­‐energy  change  of  a  reac8on  tells   us  whether  or  not  the  reac8on  occurs   spontaneously     Biologists  want  to  know  which  reac8ons  occur   spontaneously  and  which  require  input  of   energy   To  do  so,  they  need  to  determine  energy   changes  that  occur  in  chemical  reac8ons    Free-­‐Energy  Change,  ΔG   A  living  systemʼs  free  energy  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,  or  change  in   total  energy  (∆H),  change  in  entropy  (∆S),  and   temperature  in  Kelvin  units  (T)            ∆G  =  ∆H  -  T∆S   Only  processes  with  a  nega8ve  ∆G  are   spontaneous   Spontaneous  processes  can  be  harnessed  to   perform  work   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    Figure  8.5   More free energy (higher G) Less stable Greater work capacity In a spontaneous change The free energy of the system decreases (∆G < 0) The system becomes more stable The released free energy can be harnessed to do work Less free energy (lower G) More stable Less work capacity (a) Gravitational motion (b) Diffusion (c) Chemical reaction  More free energy (higher G) Figure  8.5a   Less stable Greater work capacity In a spontaneous change The free energy of the system decreases (∆G < 0) The system becomes more stable The released free energy can be harnessed to do work Less free energy (lower G) More stable Less work capacity  Free  Energy  and  Metabolism   The  concept  of  free  energy  can  be  applied  to   the  chemistry  of  life’s  processes   Exergonic  and  Endergonic  Reac;ons  in   Metabolism   An  exergonic  reacAon  proceeds  with  a  net   release  of  free  energy  and  is  spontaneous   An  endergonic  reacAon  absorbs  free  energy   from  its  surroundings  and  is  nonspontaneous   Figure  8.6   (a) Exergonic reaction: energy released, spontaneous Reactants Amount of energy Free energy released Energy (∆G < 0) Products Progress of the reaction (b) Endergonic reaction: energy required, nonspontaneous Products Amount of Free energy energy required Energy (∆G > 0) Reactants Progress of the reaction  Equilibrium  and  Metabolism   Reac8ons  in  a  closed  system  eventually  reach   equilibrium  and  then  do  no  work    Figure  8.7   ∆G < 0 ∆G = 0  ATP  powers  cellular  work  by  coupling   exergonic  reac8ons  to  endergonic   reac8ons   A  cell  does  three  main  kinds  of  work   – Chemical   – Transport   – Mechanical   To  do  work,  cells  manage  energy  resources  by   energy  coupling,  the  use  of  an  exergonic   process  to  drive  an  endergonic  one   Most  energy  coupling  in  cells  is  mediated  by   ATP    The  Structure  and  Hydrolysis  of  ATP   ATP  (adenosine  triphosphate)  is  the  cellʼs   energy  shu>le   ATP  is  composed  of  ribose  (a  sugar),  adenine   (a  nitrogenous  base),  and  three  phosphate   groups   Figure  8.9   Adenine Triphosphate group Ribose (3 phosphate groups) (a) The structure of ATP Adenosine triphosphate (ATP) H 2O Energy Inorganic Adenosine diphosphate phosphate (ADP) (b) The hydrolysis of ATP    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    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   reac8on  of  ATP  hydrolysis  can  be  used  to  drive   an  endergonic  reac8on   Overall,  the  coupled  reac8ons  are  exergonic      ATP  drives  endergonic  reac8ons  by   phosphoryla8on,  transferring  a  phosphate   group  to  some  other  molecule,  such  as  a   reactant   The  recipient  molecule  is  now  called  a   phosphorylated  intermediate    NH3 NH2 Figure  8.10   Glu Glu ∆GGlu = +3.4 kcal/mol Glutamic acid Ammonia Glutamine (a) Glutamic acid conversion to glutamine NH3 1 P 2 ADP NH2 ADP Pi Glu ATP Glu Glu Glutamic acid Phosphorylated Glutamine intermediate (b) Conversion reaction coupled with ATP hydrolysis ∆GGlu = +3.4 kcal/mol NH3 NH2 Glu ATP ADP Pi Glu ∆GGlu = +3.4 kcal/mol ∆GATP = −7.3 kcal/mol + ∆GATP = −7.3 kcal/mol Net ∆G = −3.9 kcal/mol (c) Free-energy change for coupled reaction    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    Transport protein Solute Figure  8.11   ATP ADP Pi P Pi Solute transported (a) Transport work: ATP phosphorylates transport proteins. Vesicle Cytoskeletal track ATP ADP Pi ATP Motor protein Protein and vesicle moved (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.  The  Regenera8on  of  ATP   ATP  is  a  renewable  resource  that  is   regenerated  by  addi8on  of  a  phosphate  group   to  adenosine  diphosphate  (ADP)   The  energy  to  phosphorylate  ADP  comes  from   catabolic  reac8ons  in  the  cell   The  ATP  cycle  is  a  revolving  door  through   which  energy  passes  during  its  transfer  from   catabolic  to  anabolic  pathways    Figure  8.12   ATP H 2O Energy from Energy for cellular catabolism work (endergonic (exergonic, energy- ADP Pi energy-consuming releasing processes) processes)  Organiza8on  of  the  Chemistry  of  Life   into  Metabolic  Pathways   A  metabolic  pathway  begins  with  a  specific   molecule  and  ends  with  a  product   Each  step  is  catalyzed  by  a  specific  enzyme    Figure  8.UN01   Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Reaction 2 Reaction 3 Starting Product molecule   Enzymes  speed  up  metabolic   reac8ons  by  lowering  energy  barriers   A  catalyst  is  a  chemical  agent  that  speeds  up  a   reac8on  without  being  consumed  by  the   reac8on   An  enzyme  is  a  cataly8c  protein   Hydrolysis  of  sucrose  by  the  enzyme  sucrase  is   an  example  of  an  enzyme-­‐catalyzed  reac8on    Figure  8.UN02   Sucrase Sucrose Glucose Fructose (C12H22O11) (C6H12O6) (C6H12O6)  The  Ac8va8on  Energy  Barrier   Every  chemical  reac8on  between  molecules   involves  bond  breaking  and  bond  forming   The  ini8al  energy  needed  to  start  a  chemical   reac8on  is  called  the  free  energy  of  ac8va8on,   or  acAvaAon  energy  (EA)     Ac8va8on  energy  is  oMen  supplied  in  the  form   of  thermal  energy  that  the  reactant  molecules   absorb  from  their  surroundings    A B Figure  8.13   C D Transition state A B EA Free energy C D Reactants A B ∆G < O C D Products Progress of the reaction  How  Enzymes  Speed  Up  Reac8ons   Enzymes  catalyze  reac8ons  by  lowering  the   EA  barrier   Enzymes  do  not  affect  the  change  in  free   energy  (∆G);  instead,  they  hasten  reac8ons   that  would  occur  eventually    Course of Figure  8.14   reaction EA without without enzyme enzyme EA with enzyme is lower Free energy Reactants Course of ∆G is unaffected reaction by enzyme with enzyme Products Progress of the reaction  Substrate  Specificity  of  Enzymes   The  reactant  that  an  enzyme  acts  on  is  called   the  enzymeʼs  substrate     The  enzyme  binds  to  its  substrate,  forming  an   enzyme-­‐substrate  complex   The  reac8on  catalyzed  by  each  enzyme  is   very  specific      The  acAve  site  is  the  region  on  the  enzyme   where  the  substrate  binds  (Lock  and  Key)   Induced  fit  of  a  substrate  brings  chemical   groups  of  the  ac8ve  site  into  posi8ons  that   enhance  their  ability  to  catalyze  the  reac8on    Figure  8.15   Substrate Active site Enzyme Enzyme-substrate complex  Catalysis  in  the  Enzyme’s  Ac8ve  Site   In  an  enzyma8c  reac8on,  the  substrate  binds   to  the  ac8ve  site  of  the  enzyme   The  ac8ve  site  can  lower  an  EA  barrier  by   – Orien8ng  substrates  correctly   – Straining  substrate  bonds   – Providing  a  favorable  microenvironment   – Covalently  bonding  to  the  substrate    Effects  of  Local  Condi8ons  on  Enzyme   Ac8vity   An  enzyme’s  ac8vity  can  be  affected  by   – General  environmental  factors,  such  as   temperature  and  pH   – Chemicals  that  specifically  influence  the  enzyme    Effects  of  Temperature  and  pH   Each  enzyme  has  an  op8mal  temperature  in   which  it  can  func8on   Each  enzyme  has  an  op8mal  pH  in  which  it  can   func8on   Op8mal  condi8ons  favor  the  most  ac8ve   shape  for  the  enzyme  molecule    Optimal temperature for Optimal temperature for typical human enzyme enzyme of thermophilic (37°C)  17   (heat-tolerant) Rate of reaction Figure bacteria (77°C) 0 6020 40 80 100 120 Temperature (°C) (a) Optimal temperature for two enzymes Optimal pH for pepsin Optimal pH for trypsin (stomach (intestinal enzyme) enzyme) Rate of reaction 0 1 5 26 3 4 7 8 9 10 pH (b) Optimal pH for two enzymes  Figure  8.17a   Optimal temperature for Optimal temperature for typical human enzyme enzyme of thermophilic (37°C) (heat-tolerant) bacteria (77°C) Rate of reaction 0 20 40 60 80 100 120 Temperature (°C) (a) Optimal temperature for two enzymes  Figure  8.17b   Optimal pH for pepsin Optimal pH for trypsin (stomach (intestinal enzyme) enzyme) Rate of reaction 0 1 2 3 4 5 6 7 8 9 10 pH (b) Optimal pH for two enzymes  Cofactors   Cofactors  are  nonprotein  enzyme  helpers   Cofactors  may  be  inorganic  (such  as  a  metal  in   ionic  form)  or  organic   An  organic  cofactor  is  called  a  coenzyme   Coenzymes  include  vitamins    Enzyme  Inhibitors   CompeAAve  inhibitors  bind  to  the  ac8ve  site   of  an  enzyme,  compe8ng  with  the  substrate   NoncompeAAve  inhibitors  bind  to  another   part  of  an  enzyme,  causing  the  enzyme  to   change  shape  and  making  the  ac8ve  site  less   effec8ve   Examples  of  inhibitors  include  toxins,  poisons,   pes8cides,  and  an8bio8cs    Figure  8.18   (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Competitive inhibitor Enzyme Noncompetitive inhibitor  The  Evolu8on  of  Enzymes   Enzymes  are  proteins  encoded  by  genes   Changes  (muta8ons)  in  genes  lead  to  changes   in  amino  acid  composi8on  of  an  enzyme   Altered  amino  acids  in  enzymes  may  result  in   novel  enzyme  ac8vity  or  altered  substrate   specificity   Under  new  environmental  condi8ons  a  novel   form  of  an  enzyme  might  be  favored   – For  example,  six  amino  acid  changes  improved   substrate  binding  and  breakdown  in  E.  coli    Regula8on  of  enzyme  ac8vity  helps   control  metabolism   Chemical  chaos  would  result  if  a  cell’s   metabolic  pathways  were  not  8ghtly   regulated   A  cell  does  this  by  switching  on  or  off  the   genes  that  encode  specific  enzymes  or  by   regula8ng  the  ac8vity  of  enzymes    Allosteric  Regula8on  of  Enzymes   Allosteric  regulaAon  may  either  inhibit  or   s8mulate  an  enzymeʼs  ac8vity   Allosteric  regula8on  occurs  when  a  regulatory   molecule  binds  to  a  protein  at  one  site  and   affects  the  proteinʼs  func8on  at  another  site    Allosteric  Ac;va;on  and  Inhibi;on   Most  allosterically  regulated  enzymes  are   made  from  polypep8de  subunits   Each  enzyme  has  ac8ve  and  inac8ve  forms   The  binding  of  an  ac8vator  stabilizes  the   ac8ve  form  of  the  enzyme   The  binding  of  an  inhibitor  stabilizes  the   inac8ve  form  of  the  enzyme   (a) Allosteric activators and inhibitors (b) Cooperativity: another type of allosteric activation Figure  8.20   Allosteric enzyme Active site with four subunits (one of four) Substrate Regulatory site (one Activator of four) Active form Stabilized Inactive form Stabilized active form active form Oscillation Non- functional active site Inhibitor Inactive form Stabilized inactive form    CooperaAvity  is  a  form  of  allosteric  regula8on   that  can  amplify  enzyme  ac8vity   One  substrate  molecule  primes  an  enzyme  to   act  on  addi8onal  substrate  molecules  more   readily   Coopera8vity  is  allosteric  because  binding  by  a   substrate  to  one  ac8ve  site  affects  catalysis  in   a  different  ac8ve  site    Feedback  Inhibi;on   In  feedback  inhibiAon,  the  end  product  of  a   metabolic  pathway  shuts  down  the  pathway   Feedback  inhibi8on  prevents  a  cell  from   was8ng  chemical  resources  by  synthesizing   more  product  than  is  needed    Active site available Threonine in active site Figure  8.21   Enzyme 1 (threonine Isoleucine deaminase) used up by cell Intermediate A Feedback inhibition Active site no Enzyme 2 longer available; Intermediate B pathway is halted. Enzyme 3 Intermediate C Isoleucine binds to Enzyme 4 allosteric site. Intermediate D Enzyme 5 End product (isoleucine)  Localiza8on  of  Enzymes  Within  the   Cell   Structures  within  the  cell  help  bring  order  to   metabolic  pathways   Some  enzymes  act  as  structural  components   of  membranes   In  eukaryo8c  cells,  some  enzymes  reside  in   specific  organelles;  for  example,  enzymes  for   cellular  respira8on  are  located  in   mitochondria    Course of Figure  8.UN04   reaction EA without without enzyme enzyme EA with enzyme is lower Free energy Reactants Course of ∆G is unaffected reaction by enzyme with enzyme Products Progress of the reaction