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The Diauxic Growth Curve of E. coli grown in limiting concentrations of a mixture of glucose and lactose Jt 2&33E33_B  s *޽h ? f3f3ff tl@ (  `  c 8ARegfig10s  6,7d ?"0  v1 cAMPNCAP~T0 2 S_cAMPNCAP YTir~T(W/TRP[ N,RNApolase MbN/TRP[~T lU_ۏL0 3 S_:\cAMPTCAPe, RNApolase NN/TRP[~T0 Q  2 2333/333333    x  6Gd ?"  Figure 10. Catabolite repression is positive control of the lac operon. The effect is an increase in the rate of transcription. " 2`Z> ';B  s *޽h ? f3f3ff P^(  &  6Xd ?"c  & ga|e   cAMPvNuSa|b6R0 a|Mirb6RzxsSvv;m'` cAMPSm^ NM cAMP NNCAP~T RNAYZv N~T lU_ NۏL0 ea|e   cAMPSm^ NGS cAMPNCAP(Mirvo;mˆ}v)~T,N/TRWV~T lU_ۏL.   2$3& 3A$3& 35$3 33  B  s *޽h ? f3f3ff! 6!.!`EE$ (  $ $ 0T   d1 X[(W[ire mRNA_0RlU_ WV c6RR ~gWV P P R t O z y a t -JSsN|v nv lYNpWv [ir ;Oir 1Y;m;Oir RNAYZv cAMP CRP n, @ZG ]&&(',&b$-?< XJ O1]emu C$ c $P&d@  d hsN|d~P[ 1$8 @ E$ fr $ 6Zp <fr $ 6Z  <@ n  D$@N  ^ p  $ n TB  $ c $D00TB  $ c $D0TB  $ c $DP0PTB $ c $DZB $ s *D ZB $ s *D PPTB $ c $DppTB $ c $DTB $ c $D  TB $ c $DTB $ c $DTB $ c $DTB $ c $DppZ $ s *pPZ $ s *p0PZB $ s *D0 ZB $ s *D0P PZ2 $ s *`Pfr $ 6Z^Z2 $ s *pZ2 $ s *t  $ DB CDElF[[@ $0Hpppp0pPppppp0pPpppp0Ppppp0pPppppp0pPpppp0`0Ppppp 0Xp ppp 0 X p   P p p p  8 P `p p x p?@@                              `@ !$ BC0DE4F 0 @`000 @`0 @    @ZB "$ s *D@Z #$ s * 0Z2 $$ s *PPZB %$B s *D0`ZB &$ s *D0PZ2 '$ s * ` ($ 0BtdZR )$ s *DXN @ *$ 0ZR +$ s *D@lR ,$ <G%@lR -$ <G&0TB .$B c $D0TB /$ c $DZR 0$ s *@p&N v @  1$ `*p`r 2$B 0G @ `r 3$ 0Gv  ZB 4$ s *D @ 0ZB 5$ s *D@PZB 6$ s *D@0ZB 7$ s *D0ZB 8$ s *DZB 9$ s *D`` :$ 0  Z2 ;$ s * p Z <$ s *p 0 &N 0 @  =$ p : `r >$B 0G @ `r ?$ 0G0 @ f" @$ 6G$ p  ` A$ 00 Z2 B$ s * L  $ 6  z sN|d~P[&(LB $ c $DppLB $ c $DdR $ <G%p   $ 0بp`j  vDNA RNA ˆ}v(( 2 & B $ s *޽h ? f3f3ffz  *"((((  (~ ( s *XHP     ( <P    L8XJ O1]emu*8 .  ((P@@ TB ( c $DPTB  ( c $D@@P* @ .  '(. TB ( c $D@@P~ @ .  &(. TB ( c $DPZB ( s *DpZB  ( s *D p Z ( s *@ ZB ( s *DZB ( s *D   @ .  %(. TB ( c $DpTB ( c $Dp  TB  ( c $DPTB  ( c $D  PTB  ( c $DPTB ( c $DPTB ( c $DPZ ( s *@ Z2 ( s *p0` fr ( 6Z.pZ2 ( s *pP`@Z2 ( s *p` ( BC0DE4F 0 @`000 @`0 @    ZB ( s *DPPZ ( s * ` Z2 ( s *   ZB (B s *D0  ZB ( s *D  Z2 ( s *p  `  ( 0D 4 ZR !( s *&N 0 @  "( p :` `r #(B 0G @ `r $( 0G0 @ B ( s *޽h ? 33̙3   t l , (  ,~ , s *h@      , 0` 0  3 NX[(W[ire mRNAellU_ WV c6RR ~gWV P P R t O z y a t `-0Z$Z0ZP&'&, $68XJ O1]emuLB , c $D00LB , c $D 0 LB , c $D0LB , c $DRB , s *D   RB  , s *D LB  , c $DppLB  , c $DLB  , c $D LB  , c $DLB , c $DLB , c $DLB , c $DppR , s * pR , s * p0RB , s *D 0  RB , s *D0 R2 , s *^r , 6ZR2 , s *R2 , s * , BC0DE4F 0 @`000 @`0 @    @@R , s *RR , s *D@jR , BG @ B , s *޽h ? 33̙3 p06(  0b 0 c :AlacoperonF 0 6@ ?" 5 This assortment of genes and their regulatory regions is called the Lac operon. The Lac operon has been examined in detail. Here is a diagram of it: 2 2D I4H 8B 0 s *޽h ? f3f3ff  +,4R(  4L  4# BN  4 N   4   4 B< ?"  GElement$t 4 6 ?" N   4    4 B ?"  Gpurpose$t  4 6 ?" N  @  4  @  4 B ?" @ cOperator (LacO) t  4 6 ?" @N  @ 4  @ 4 B ?" @ Lbinding site for repressort 4 6 ?" @N @` 4 @` 4 B  ?"@` cPromoter (LacP) t 4 6 ?"@`N @` 4 @` 4 B ?"@` Qbinding site for RNA polymerase t 4 6 ?"@`N ` 4 ` 4 B ?"` dRepressor (LacI) t 4 6 ?"`N ` 4 ` 4 B ?"` w#gene encoding lac repressor protein$$t 4 6 ?"`N  4  4 B ?" {IBinds to DNA at operator and blocks binding of RNA polymerase at promoterJJt 4 6 ?"N   4  !4 B ?" 4Pit "4 6 ?"N  #4  $4 B ?" epromoter for LacI t %4 6 ?"N  &4  '4 B ?" 5CAPt (4 6 ?"N  )4  *4 B ?" u!binding site for cAMP/CAP complex"" t +4 6 ?"t ,4 6 h+?"B 4 s *޽h ? f3f3ff  8M(  8N 8 C &A laconl`P 8  0x   GWhen lactose is present(H 8 0޽h ? f3f3ff @Q(  @P @ C (Alacoff`Pe @ c $,`   U%When the inducer (lactose) is removed&& H @ 0޽h ? f3f3ff%  He(  HR H C *Alacgluc^ H  0tjP   j [+When levels of glucose in the cell are high,,H H 0޽h ? f3f3ff0 x(  ^ S    r c $t @    Catabolite Repression Enzyme Induction is still considered a form of negative control because the effect of the regulatory molecule (the active repressor) is to decrease or downregulate transcription. Catabolite repression is a type of positive control of transcription, since a regulatory protein affects an increase (upregulation) in the rate of transcription of an operon. The process was discovered in E. coli and was originally referred to as the glucose effect because it was found that glucose repressed the synthesis of certain inducible enzymes, even though the inducer of the pathway was present in the environment. The discovery was made during study of the regulation of lac operon in E. coli. Since glucose is degraded by constitutive enzymes and lactose is initially degraded by inducible enzymes, what would happen if the bacterium was grown in limiting amounts of glucose and lactose? A plot of the bacterial growth rate resulted in a diauxic growth curve which showed two distinct phases of active growth (Figure 9). During the first phase of exponential growth, the bacteria utilize glucose as a source of energy until all the glucose is exhausted. Then, after a secondary lag phase, the lactose is utilized during a second stage of exponential growth. Figure 9. The Diauxic Growth Curve of E. coli grown in limiting concentrations of a mixture of glucose and lactose During the period of glucose utilization, lactose is not utilized because the cells are unable to transport and cleave the disaccharide lactose. Glucose is always metabolized first in preference to other sugars. Only after glucose is completely utilized is lactose degraded. The lactose operon is repressed even though lactose (the inducer) is present. The ecological rationale is that glucose is a better source of energy than lactose since its utilization requires two less enzymes. Only after glucose is exhausted are the enzymes for lactose utilization synthesized. The secondary lag during diauxic growth represents the time required for the complete induction of the lac operon and synthesis of the enzymes necessary for lactose utilization (lactose permease and beta-galactosidase). Only then does bacterial growth occur at the expense of lactose. Since the availability of glucose represses the enzymes for lactose utilization, this type of repression became known as catabolite repression or the glucose effect. Glucose is known to repress a large number of inducible enzymes in many different bacteria. Glucose represses the induction of inducible operons by inhibiting the synthesis of cyclic AMP (cAMP), a nucleotide that is required for the initiation of transcription of a large number of inducible enzyme systems including the lac operon. The role of cyclic a cAMP is complicated. cAMP is required to activate an allosteric protein called CAP (catabolite activator protein) which binds to the promoter CAP site and stimulates the binding of RNAp polymerase to the promoter for the initiation of transcription. Thus to efficiently promote gene transcription of the lac operon, not only must lactose be present to inactivate the lac repressor, but cAMP must be available to bind to CAP which binds to DNA to facilitate transcription. In the presence of glucose, adenylate cyclase (AC) activity is blocked. AC is required to synthesize cAMP from ATP. Therefore, if cAMP levels are low, CAP is inactive and transcription does not occur. In the absence of glucose, cAMP levels are high, CAP is activated by cAMP, and transcription occurs (in the presence of lactose). Many positively controlled promoters, such as the lac promoter, are not fully functional in the presence of RNAp alone and require activation by CAP. CAP is encoded by a separate Regulatory gene, and is present in constitutive levels. CAP is active only in the presence of cAMP. The binding of cAMP to CAP causes a conformational change in the protein allowing it to bind to the promoter near the RNAp binding site. CAP can apparently interact with RNAp to increase operon transcription about 50-fold. Positive control of the lac operon is illustrated in Figure10. Figure 10. Catabolite repression is positive control of the lac operon. The effect is an increase in the rate of transcription. As a form of catabolite repression, the glucose effect serves a useful function in bacteria: it requires the cells to use the best available source of energy. For many bacteria, glucose is the most common and readily utilizable substrate for growth. Thus, it inhibits indirectly the synthesis of enzymes that metabolize poorer sources of energy.  !(Y'=0&`Z`ZE`Zt5*"g6Y`Z^<   l $"h Je&F H   ,   Vk 4m7]%k6b/ 5 + & G EH  0޽h ? ̙33l0 ,$ (   ^  S      c $<* @   faIN O_uirHQ)R(usX-N[f)R(uvn dk:g6RO_uir(WNUOAQsX-NNg'Y^A~k0 42  4H  0޽h ? ̙33 0 RJ<(  <^ <S    D <c $le @   lSo let's look at the lac operon in action. When lactose is present, it acts as an inducer of the operon. It enters the cell and binds to the Lac repressor, inducing a conformational change that allows the repressor to fall off the DNA. Now the RNA polymerase is free to move along the DNA and RNA can be made from the three genes. Lactose can now be metabolized. P 2 kH < 0޽h ? ̙33 0 D'(  D^ DS     Dc $p @   =When the inducer (lactose) is removed, the repressor returns to its original conformation and binds to the DNA, so that RNA polymerase can no longer get past the promoter. No RNA and no protein is made. Note that RNA polymerase can still bind to the promoter though it is unable to move past it. That means that when the cell is ready to use the operon, RNA polymerase is already there and waiting to begin transcription; the promoter doesn't have to wait for the holoenzyme to bind. We could say that the operon is primed for transcription upon the addition of lactose. $>3k S v B =H D 0޽h ? ̙33 0  L((  L^ LS     Lc $ @    H L 0޽h ? ̙33rT0M?  &*?@ABCDEFGHIJKLMNOPRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~Root EntrydO)PicturesqCurrent UserSummaryInformation(QPowerPoint Document(QDocumentSummaryInformation8