підручники. біохімія / Uchebnik_po_Biokhimii_E_S_Severin
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H 28S H OKOJIO 50 pa3JIJfqHblX 6eJIKOB.
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B. CHHTE3 IIOJillllEITTll,lJ,HOH UEIIll
HA PHEOCOME
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6onee 700 HYKJieOTMAOB.
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cy6'heAHHHIIhIH o6pa30BaHHe 80S pH60COMbl 3a cqfa fMAPOJIH3a IT<D AO f.[J,<1> 11 tteopraH~ecKoro
<Pocct>arn. IIpH 3TOM ¢opMHPYJOTC51 A- 11 P-uem- PhI p116ocoMhI, rrp11qeM B P-uettTPe OKa3brnaeTc51 AUG-KOAOH MPHK c np11coe,i::i:11tteHHoi1: K HeMy
MeT-TPHK. Mer.
B KJieTK~x ecTh 2 pa3JI11qa10m11ec51 no CTPYKTYpe TPHK, y1Ha10m11e KOAOH AUG. 11HHIIHHpyI01UHH KOAOH y1Hafa TPHK;MeT, a TPHITJieTbI MPHK, KOLJ.MPYIOlUHe BKJIIOqeHHe MeTHOHHHa BO BttyTPeHHMe yqaCTKH 6eJIKa, rrpoqHTbIBaIOTC51 APYfOM TPHKMer.
2. :iJAOlllllU,UJI
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175
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IF-2·1T<t>-Mer-TPHKMei |
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elF-2·rTC!).MeT-TPHK Mer |
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elF-3 |
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P1116ocoMaflbHaH |
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cy6be.Q111H111L1a |
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elF-2 |
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PHC. 4-37. 06pa30B8Hlo!e HHHl..llllHpyt01J.1ero KOMnneKCB B XOAe ClllHTe3a 6enKa y 3YKBpHOTOB. Mer-TPHK,Me; 06b8AlllHfl8TCfl c Manoi1 cy6b8AlllHlllL\8i1 p11160COMbl B cpopMe rpoi1Horo KOMnneKca: Mer-rPHKM'',elF-2 Ill rTcD. 06pa30BaBWllli1Cfl 6onee CnQ)KHbli1 'l8Tb1pexKOMnOH8HTHbli1 KOMnneKC np111C08AlllHfl8TCfl K 5'-KOHL\YMPHK c nOMOlljblO H8CKOnbKlllX AOnOnHlllTenbHblX cj:laKTopoB, Ill Manafl cy6b8AlllHlllL\a Ha'l1<1HaeTCKOnb3111Tb no MPHK AO Tex nop, noKa aHTlllKOAOH Mer-rPHKMe; He CBfl)f(8TCfl c lllHlllL\llllllPYIOlJ1111M KOAOHOM AUG. np111 3TOM B KOMnneKce npOlllCXOAlllT 1113M8H8Hlll8 cocrasa lllHlllL\llllllPYIOlJ1111X cpaKTopos. Ill YCKOpfl8TCfl np111C08AlllH8Hlll8 60S cy6b8AlllHlllL\bl p11160COMbl,
Mer-rPHK,''e'3aH1<1Maer Ha p1116oc0Me P-L18HTp.
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a-NH 2-rpynne |
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a11.111ttoau11JJbttoro ocTaTKa aa-TPHK A-uettTpa |
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c o6pa30llaJll1CM HOBOM nenT!11lHOH CB51'3!1; |
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176
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5'
rT<l>·EF-1 AMlllHOat.t111n-TPHK EF-1 JA<ll
PMC. 4-38. BKnto'leHMeaa1·TPHK···B p1116oc0My. aa,-TPHK···B3al1MOAeiiicTByeT c p1160COMOiii B B11A8 TpOiiiHOro KOMnneKca, COCTOS1lJ.\8rO 113 rpaKrnpa an0Hra1.11111 EF-1, aa,-TPHK••· 11 rT<P. AHrnKOAOH aa-TPHK••• KOMnneMeHrnpeH 11 aHrnnapanneneH KOAOHY MPHK BA- 1.18HTpe. CBS13blBaH11e aa,-TPHK""'npOl1CXOAl'!T3a C4eT :3Heprn11 rn11pon113a rT<P AO rD<P 11 P,.
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TPHK'-0 |
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TPHK"-0 |
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TPHK'-0 |
TPHK"-0 |
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I |
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I |
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I |
I |
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~A+ ~A~ ~A+ ~-A |
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0 |
OH |
0 |
OH |
OH OH |
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0 |
OH |
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o=6I |
~6=oI |
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I |
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( |
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C=O |
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CH-S-(CH) -CH |
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R'-CH |
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R'-CH |
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3 |
2 2 |
I |
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I |
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I |
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NH2 |
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NH2 |
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NH |
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I |
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C=O |
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I |
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CH - S- ( CH ) |
- CH |
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3 |
2 2 |
I |
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NH2 |
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P111c. 4·39. PeaKl.IMSI |
TpaHcnenTMAa1.1111111. MeT110Hl1H OT |
MeT-TPHK,Mer, HaXOAS1ll.\8r0CS1 B P-1.1eHTpe, np11coe1111HsieTcsi |
K rx-NH 2-rpynne |
aM11Hoa1.111nbHOro OCTaTKa aa,-TPHK···A-1.1eHTpa c o6pa30BaH118M HOBOiii nem1111Hoiii CBS1311.
118,ll.alOUiafl CBOHCTBaMH ¢epMeHTOB. 3TH KaTaJJHTWieCKH aKTHBHble PH K nOJIY'!l1Jil1 tta3BaH11e p1160J11MOB (CM. pa3,ll,eJI 2). noJiaraIOT, 'HOp1160311Mbl MO)l(HO cql1T3Tb «peJil1KT3Ml1» paHHero nepHO,lla 3BOJIJOUl1l1, KOf,ll3 6eJIKl1 ewe He np:1106peJil1 TaKOrO 3Haqemrn, KaK B nocJie,lly10m:11e nep:110,Libl.
TpeTbfl cTa,rrHfl 3JIOHrau11:11. K p:116oc0Me np:11coen11HHeTcf! ¢aKrnp 3;1ourau11tt
11 Ja cYeT 3Heprn11 fT<ll npo,LIB11raeT p116oc0My no
MPHK tta O,LIHH KO,llOH K 3'-Kouuy. B peJyJlhTaTe ,UttnenTl1,ll,11JI-TPHK, KOTOpafl He MeHf!eT CBOero noJIO)l(eHHfl OTHOC11TeJibHO MPHK, :113 A-uettTpa nepeMemaeTcfl B P-uettTp. Cso6o,LIHafl OT MeT:11ou:11tta
TPH KMCT nOKH,llaeT ptt6ocoMy, a B o6JiacTb A-ueHT- pa no~arraeT CJie,UyI01Ul1H KO,LIOH (pl1C. 4-40).
no 3aBepweHl1H TpeTbeH CTa,lll111 3JIOHf3Ul1V! pvr60COM3 B P-uettTpe HMeeT ,llvrnenrn,LIHJI-TPH K, a s A-uettTp nonarraeT Tp11nJieT, Ko,Livrpy10uu1~i BKJIIO-
177
A-L\8HTp CB060ABH
rPHK |
nenrnAi.m-rPH K |
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~ |
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rTcD |
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\EF-2 |
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P-L\8HTp |
A~"e"'~• |
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jl - J ___ l ___ 3' |
5'___L_ |
3' |
rPHK
+
MPHK
+
P,
PMc. 4-40. CTaAMsi rpaHc110KaL1MM. K p1116oc0Me np111coe11111Hsiercsi cjJaKTop 3n0Hra4111111 EF-2, 111 3a C'leT3Heprn111 IT© npo11s111raer p11160c0My no MPHK Ha OAlllH KOAOH K 3'-KOH4Y-nenrn11111n-TPHK, He MeH5151 csoero nono)KeHlll51 OTHOClllTenbHO MPHK, 1113 A-4eHTpa nepeMeU1aeTC51 s P-4eHTp.
'ICHl1ell no;rnnenTl1,LIHYIO uenb BTOpoti aMl1HOKl1CJTOTbl. Ha<JHHaeTc51 cJTe,Liy10ur11tl u11KJ1 cTa,LI1111 'JJTOHrau1111, s xone KOToporo Ha p116oc0Me cHosa npo- xo,LI51T Bb!WeOn11caHHble C06b!Tl151. noBTOpe1-111e TaKHX U,11KJlOB no '111CJ1YCMbICJTOBblX KOllOHOU rvt PH K JaBepwaeT secb 3Tan 3J10Hrau,1111_
3. TepMUHaU,UR
TepM11Hau1151 TpaHCJT51U1111 HaCTynaeT B T0\1 rnyYae, Kor,Lia B A-ueHTp p116oc0Mbl nona11acT 01111H 113 CTOfl-KO)lOHOB: UAG, UAA 11.Jll1 UGA. Ll,JT51 CTOflKO)lOHOB HeT coorneTcTBy10ur11x TPH K. BMecTo :noro K p116oc0Me np11coe1111H5llOTC51 2 6eJTKOBblX BblCB060)(()laIOW,11X cpaKTopa RF (OT aHrn. releasingf'actor)
11.Jll1 <j>aKTOpa TepMHHaU,UH. 01111H 113 H 11X c fTOMOllJ,blO nenTl1)111JTTpaHccpepa3HOIO UCf!Tpa KaT<U111Jl1pyeT r11J1pomnw1ecKoe 0Tw,em1eH11e c11HTeJ11posaHHOro nem1111a OT TPHK. Ll,pyrotl Ja C'IeT:rncpr1111 rn11poJT113a fT<D Bb!JbIBaeT 1111CCOU11aUl110 p116ocoMbI Ha cy6nen11H11uhr (p11c.
VIHTcpecHo OTMeTl1Th, 'ITOcpaKTopb1 TpaHCJT5tu1111, pe<Uil13YIOUI11e 3cpcpeKTbI Ja CYeT rn11poJT113a fT<D, 5IBJUHOTC51 YJ1eHaM11 cynepceMetlcrna G-6eJTKOB, B KOTopoe BX01151T G-6eJTKl1, yyacrnyIOur11e B TpaHcJlYKUl111 ClffH<VlOB ropMOHOB 11 11pyrnx 6110.JlOrHYeCKH aKTl1BHbIX Bew,ecrn, 11 Ras-6eJTKl1, cpyHKu110H11py10w,11e KaK cpaKTophI poem (cM. pa311eJTh1 II, 15).
Bee G-6eJTKl1 CB513hIBalOT 11 rn11poJTHJyIOT rT<D. Koma 0H11 CB513aHhI c fT<D, rn aKT11Bttb1 11 yYaCTBYIOT B COOTBeTCTBYIOUI11X MeTa6oJTWieCKl1X
npoueccax. a KOIJta B aKTHBHOM ueHTpe B pe3yJThTme nmpo;1113a IT<D 11penpawaeTc5l B fLl,<D, 3Tl1 6e;1Kl1 npv106peTalOT HeaKTl1BHYIO KOHcpOpMaU,11IO.
TaK11M o6pa3oM, MaTpW1Ha5l np11po.Lla npouecca TpaHCJT51Ul111 npOs-!llJTs-JeTCs-J ll TOM, '!TO flOCJTe)lOBaTCJlbHOCTb nocry1rneH115l aM11Hoaw1JT-TPH K B p116oc0My wrn CHHTeJa 6eJTKa CTporo JlCTepM11Hl1posaHa MPHK. T.c. 110p5!1IOK pacnoJTO)f(eH115l KO- l!OHOB B.ilOJTh uenv1 MPH K on.HOJHaYHo JanaeT crpyKTYPY CHHTC311pyeMoro 6eJTKa. P116oco1vta CKaHHpyer uenb MPHK B B11ne Tp11nJTeTOB H nocJTenoBaTeJTbHO OT611paeT H3 OKpy>KalOuretl cpe]lbl «Hy)l(- HblC» aa-rPHK, OCB060)1(Jla51 B xone 3JTOHrau1111 JJeau111111poBaHHhie rPH K.
M<rnas1 11 6oJTbwaH cy6bel!HHHUbl p116oc0Mb1 B npm1ecce TpaHCJl5IUl111 Ubll10JIH5llOT pa3HblC cpyHKu1111: M<UJ<UI cy6be,LI11H1ma npHcoe11HH5leT MPH K H JJCKOJUtpyn 1111(!JOp:v1au1110 c noMOWblO TPHK 11 MexaHHJMa Tpa11cJTOKauvi11, a 6oJTbWa51 cy6be11111111ua OTBCTCTBCHHa Ja 06paJORaH11e nenTH)lHblX CBHJei-f.
f. fiOJU.fPHEOCOMhl
B npouecce CHHTCJa 6eJTKa pH6ocoMa np11coe- llHH5leTcs-i K 5'-KOHUY MPH K H nepeMew,aeTC51 B HaI1paBJTeHHH 3'-KOHU<l.npH )TOM 5'-KOHCI(MPHK OCR060)1()1aeTC51, 11 K HeMy MO)f(eT npHCOellHHHTbCfl HOBaf! p116oc0Ma, Ha KOTopoi-f HaY11HaeTC5I pOCT cure 011Hoi-f noJT11nenTHll.HOtl uenH. KaK npaBHJTO,
178
nenrn.QHn-rPHK |
nenrM.QHfl-TPHK |
451
1;'\
OH
I
P111c. 4-41. TepM111Ha1..1111s:i ClllHTeaa 6enKa.
+
RF-1
\
~-~-->:o-~.,~--.
..L ..J...-..l 3'
Ceo60.QHb1itl normnenrnA
P;
+
r.Q<I'
+
RF-1
-~~
RF-3
5'
MHOro pH60COM OJJ:HOBpeMeHHO yqacrnyeT B CHH-
Te3e 6e11Ka Ha OLlHOH l1 rn11 )Ke |
MPH K, o6paJyH |
KOMfIJleKC, KOTOpblH HJ3blBalOT |
nOJll1p~16ocoMOi1' |
111111 00Jll1COMOH (pl1C. 4-42). |
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Ka)((.IlaH p116oc0Ma 3aH11Mac1 |
Ha MPH K yqac- |
TOK Llfll1HOH OKOJlO 80 11y1<.neOTl1JJ,OB, fl03TOMY pM-
6ocOMbl pacnommtIOTCH Ha c mnepBaJTOM np11MepHo B 100 HyKJJeornHOB. YeM LlflHHHee no1111nenT11nHaH ueno4Ka c11HTeJ11pyeMoro 6e11Ka, TeM 60JlbWe p1160COM MO)KeT OLlHOBpeMeHHO ocyweCTBJl51Tb Cl1HTe3 3TOro 6eJIKa, 3Ha411TeJlbHO yBeJm411B<l51 TaKHM o6pa30M 3cf>cf>eKTl1BHOCTb 11CflOJlh30BaHH51 MaTpl1Ubl.
Ka)l(Lla51 p116oc0Ma cnoco6tta KaTaJTH3l1pOBaTb o6pa30BaHHe OKOJIO I00 nemHJJ:HbIX CB513eH B MHHyry. 00JTl1pi160COMbl MOryr Cyll.l,eCTBOBaTb B Bl1,ll,e qacTHU, ruiaBalOll.lHX B UHTOOJlaJMe KJJeTOK, 11JlH Moryr 6bITb CBH3aHbl c 3P. CB06onttb1e uHTon11mMaT114ecKHe no1111pH60COMHbJe 'laCTHUbI OTBeTCTBeHHbl Ja Cl1HTe3 6eJTKOB, BblflOJlHHIOll.l,HX BHyrp11KJJeT04Hbie cPYHKUH11. 001111pH60COMbl, JCCOUHHpOBaHHbie C
3P, non 3JleKTpOHHhIM MHKpOCKOflOM HMelOT BHLl «mepox0Ba10J.f» no13epxHoc111. Eemor, c11H1e311pyeMb1e «UiepoxoBaTblM» 3P, LlOJl)KHbI TpaHcnopTHpoBaTbC51 qepe3 MeM6paHy LlJ151 rnro, 4T06br OHH noc111rn11 MeCTa OKOH4aTeJTbHOH .r10KaJT11Jau11H. LDrn
179
60S 0 Cy6"lacnu-1b1 D40S
~H6oc/
5'-
KOHel..I
PacTyu.iasi no111-1nenrnAHSS1 1..1enb
A
PMC. 4-42. CMHTe3 CienKOB Ha nonMpMCiocoMHOM KOMnneKce. nsnb p1116ocoM cLti.1Tb1sat0T i.1HcpopMa1.1i.1t0, coi:ieplKa111yt0csi s MPHK.
HHX xapaKTeptto rrp11cyrcTBHe Ha N-KOHUe nm:i;epHoti:, 11JIH CHfHaJibHOti:, IIOCJie)]OBaTeJibHOCTH )J)IHHOH OT 15 )]0 30 aMHHOKHCJIOTHbIX OCTaTKOB, KOTOpasI CO)]ep)l(}IT MHOfO aMHHOKHCJIOT c rm:i;po- <Po6HbIMH pa,n;HKaJiaMH H 06ecrreq11BaeT rrpOXO)l(- )]eHHe 6eJIKa qepe3 JIHII1l)l;HblH 6HCJIOti: MeM6paH. HeK0Topb1e H3 3THX 6eJIKOB )]JIH )]aJihHeti:rnero TpaHCIIOPTa yrraKOBblBaIOTC51 arrrrapaTOM fOJih)J,)1(11 B ceKpeTOpHbie rpattyJihI.
,II;. IlOCTIPAHCJUIQHOHHbIE M0,11;H<l>HKAI.J,HH
UO~HUEIITH,lJ;HOH QEUH
IloJIHnenTH)]Hhie uenH MOfYT IIO)]BepraThC51 CTpYK'fYPHbIMMO)]H<l>HKaUHHM, JIH6o 6y~H ern.e
CB513aHHbIMH c pH60COMaMH, JIH6o IIOCJie 3aBep-
rneHHH CHHTe3a. 3TH KOH<l>OpMaUHOHHbie H CTPYKTYPHhie H3MeHeHmt: rron11nenT1l)J,Hh1x uerreti: rronyqHJIH Ha3BaHHe IIOCTTpaHCJIHUHOHHbIX H3Mettem1ti:. 0HH BKmoqaIOT y)]aJieHHe qacTH nOJIHrrerrnt)]HOti: uerrH, KOBaJieHTHOe rrpHCOe)]HHeHHe O)]HOfO 11JIH HeCKOJihKHX HH3KOMOJieKYJI51pHbIX JIHraH)]OB, npHo6peTeHHe 6eJIKOM HaTHBHOH KOH<l>opMaUHH.
Mttorne MO)]H<l>HKaJ..J.Im ocyrn.ecTBJUIIOTCH B 3P. 3)].eCb rrpoHCXO)]HT <l>OJWDll'UOJIHUelffll,MbIX u.eneit
H <J>opMHPOBaHHe YHHKaJibHOti: TpeTHqHoti: HJIH qernepT11qttoti: cTpyKTyphI 6enKoB. Ilp11qeM )]JIH no,1J.I1.epx<aHH5I HanrnHoti: KOH<l>opMaUHH MOJieKyJI orpoMHOe 3HaqeHHe HMeeT rrpaBHJibHOe <l>opMHpOBaHHe rofCYJib<l>H)]llbIX CBH3eH.
qaCTH'IHblHnpoTeOJIH3
Mttor11e 6enKH, ceKpeT11pyeMh1e 113 KJieTOK, rrepBOHaqanhHO CHHTe3HPYIOTC51 B Bm:i;e MOJieKYJI-rrpe)]- rnecTBeHHHKOB, <l>YHKUHOHaJibHO HeaKTHBHbIX.
Y)]aJiemJe qacTH rrommerrTm:i;Hoti: uerrH crreu11<1>11qecKHMH 3H)]orrpoTea3aMH rrpHBO)]HT K o6pa3oBaHHIO aKTHBHhIX MOJieKYJI. HeK0Toph1e 6enKH-rrpe)]- rnecrneHHHKH pacrn.eIIJIHIOTCH B 3P rnn1 anrrapaTe foJib)])l(H, )]pyr11e - rrocne ceKpeu1m. TaK, HeaKTHBHhie rrpe)]rnecTBeHHHKH ceKpeTHpyeMbIX <t>epMeHTOB - 3HMOfeHhl - o6pa3YIOT aKTHBHbIH <J>epMeHT nocne pacrn.ennemrn no orrpe)]eJieHHhIM yqaCTKaM MOJieKYJihl: 3HMOreH rraHKpeaT11qecKOti: )[(eJie3hl TpHIICHHOreH npeBparn.aeTC51 B aKTHBHhIH TpHnCHH nocne ceKpeUHH B TOHKHH KHllleqHHK.
HarJI51)]HhIM rrpHMepoM rrocne)]OBaTeJihttoro )]Byx- cTa,n;Hti:Horo rrpoTeOJIH3a CJIY)[(HT o6pa3oBaHHe aKTHBHhIX <t>opM rrerrTm:i;HblX ropMOHOB (HarrpHMep, HHCYJIHHa HJIH rJIIOKarotta) H3 rrperrporopMOHOB. IlepBoHaqanhHO N-KOHUeBoti: c11rnanbHh1ti: rrenTm:i; MOJieKyJihI-rrpe)]rnecTBeHHHKa y)]aJI51eTC51 B 3P B rrpouecce c11me3a 6enKa H o6paJyeTCH HeaKTHBHhiti: rrporopMOH. 3aTeM rrporopMOH B ceKpeTOpHhlX rpaHynax, <t>opMHPYIOlll.HXC51 B arrnapaTe fOJib)])l(H, nO)]BepraeTC51 )]eti:CTBHIO 3H)]O- H/HJIH 3K30npoTea3 H npeBparn.aeTC51 B aKTHBHhlti: ropMOH.
KoBaJieHTHhie MOrot<l>Hirau.nu
CTpyK'fYPHhie6eJIKH H <J>epMeHThI MOfYT aKTHBHpoBaThCH 11JIH HHaKTHBHpOBaThC51 B pe3yJibTaTe npHCOe)]HHeHH51 pa3JIHqHbIX XHMHqeCKHX rpyrrrr: <t>oc<t>aTHhlX, aUHJihHhIX, MeTHJibHhIX,'OJIHrocaxaPMHbIX 11 HeKOTOPhIX )]pyrHX.
<l>oc<t>opHJiupoBaHHe 6eJIKOB ocyrn.ecTBJUieTcH no rm:i;pOKCHJibHblM rpyrrrraM cepHHa, TpeOHHHa
180
11, pexe, T11po311Ha cl>epMeHTaMl1 113 rpyrrnhI rrpOTel1HKHHa3, Tor.ua KaK .uecl>occl>opmrnp0BaH11e KaTa.Jil1311PYlOT m.upo.Jil1TWiecKHe cl>epMeHThl cl>occl>orrpoTel1HcPOCcPaTa3hI (CM. pa3,Ue.JI 2). fJIHK03HJIHPOBaHHe. 6e.JIKH, BXO,UHI1Il1e B COCTaB IJJia3MaT11qecKHX MeM6paH HJil1 CeKPeT11pyioII1HeCH 113 KJieTOK, IIO,UBepraJOTCH r.Jil1K03HJil1poBaHl110. YrneBO.UHhie 11err11 rrp11coe.u11HHJOTCH no rH,UpOKCHJihHhlM rpyrrrraM cep11Ha HJil1 TpeOHHHa (0-r.Jil1K03HJil1POBaHHe) Jil160 acrrapamHa (N-rnHK03IDIHpOBaHHe). Ilocne.uoBaTe.JihHOe ttapaII111Batt11e yrneBO.UHOro cl>parMeHTa
rrpo11CXO.UHT B 3P 11 arrnapaTe fOJih,U)l(H. MttoroqncneHHhIM Mo.u11cl>nKa1111HM no.uBepra-
JOTCH 6oKOBbie pa,Ul1KaJihI HeKOTOpblX aMHHOKHCJIOT: B Tl1peorno6y.JI11He MO.UHPYJOTCH ocTaTKH THpo311tta; B cl>aKTopax cBepThrnatt11H KPOBl1 Kap60KCHJil1PYJOTCH OCTaTKH rnyTaMarn; B 3P cPH6po6.JiaCTOB m.upoKCHJIHPYJOTCH ocTaTKH npon11tta 11 Jil1311Ha B 11errS1x TporroKo.JIJiareHa.
VI. "1Hr"16"1TOPbl MATP"1LIHblX
6"10C"1HTE30B
CyII1eCTByeT 60.JibIIIaH rpynna BeIIIeCTB, HHm6HPYJOIIIM c11me3 ,[(HK, PHK HJIH 6e.JIKOB. HeKOTOphie 113 HHX HaIIIJil1 np11MeHeH11e B Me,U11II11He ,UJIH JieqeHHH HHcPeKIIl10HHhIX 6o.Jie3HeM 11 orryxoJieBbIX HOBoo6pa30BaH11M, a .upyr11e ,UJIH qe.JIOBeKa OKa3aJIHCh TOKCl1HaMl1.
L(e:Hcrn11e HHrH611TOPOB MaTpWIHhIX 6110CHHTe30B KaK JieKapcTBeHHhIX npenapaTOB OCHOBaHO Ha Mo.u11c1>11Ka111111 MaTp1111: ,[(HK, PHK, 6e.JIOKCHHTe3HPYJOIIIero arrrraparn (rrpe)!Ql;e Bcero, p116ocoM) IDIH Ha HHaKTHBaIIHH cl>epMeHTOB. I.l,eHTpa.JihHOe MeCTO cpe.un HHX IIPHHa,UJie)l(HT aHTH6110THKaM - pa3HOo6pa3HhIM no XHMWieCKOMy CTpOeHHJO opraHWiecKHM coe,UHHeHHHM, CHHTe311pyeMhIM MHKpoopraHH3MaMH, rJiaBHhIM o6pa30M, MHKPOCKOnJflleCKHMH rp116aM11, 11 cnoco6HbIM B Ma.JihIX KOJIWieCTBaX OKa3hIBaTh in6npaTe.JihHOe TOKCWieCKOe .ue:HCTBHe Ha
.upyr11e MHKpoopraHH3MbI (Ta6.JI.
A. HHfH:SIITOPbl PEIJJUIKAIJ,HH -
IlPOTHBOOIIYXOJIEBbIE IlPEIIAPATbl
AHT116110T11K11, B3a11Mo.uei1CTBYJOII111e c ,[(HK, HapyIIIaJOT ee MaTpWIHYJO cPYHKIIl110 H BhI3bIBaJOT rro.uaBJiett11e rrpo11eccoB pell.JI11Ka111111 11 Tpattc-
Kp11n111111. Hx 11cnOJih3YJOT ,UJIH neLJ.eHl1H 3.JIOKaqeCTBeHHhIX HOB006pa30BaH11ll 11 Ha3bIBaJOT npOTl1BoonyxoneBhIM11 npenapaTaMl1 (cM. pa3.ueJI L(ayttOM11II11H, .UOKCOpy6111111H 11 HeKOTOphie .UPYme B3al1MO,UeMCTBYJOT c MOJieKYJIOll ,[(HK TaKl1M o6pa3oM, qTo 1111Km1qecKaS1 cTpyKTypa 3Tl1X aHT116110T11KOB BCTpa11BaeTCH («HHTepKaJIHpyeT») Mex.uy napaM11 OCHOBatt11:H G=C, a yrJieBo.u- HhIH KOMilOHeHT 3aHl1MaeT MaJIYlO 6op03.UKY ,[(HK (p11c. 4-43). 3TO Be,UeT K JIOKaJihHOMY 113MeHeHl110 CTPYKTYPhI ,[(HK 11 11Hm611poBaH1110 pell.JI11Ka111111 11 TpaHCKP11IIIIl111.
K «11HTepKaJIHTOpaM» OTHOCHT Ta:JOKe aHT116110T11K aKT11HOM111111H D, 6JIOKHPYJOII111tt CHHTe3 ,[(HK 11 PHK y rrpo11 3YKap110TOB. 3TO coe.u11tteH11e CJil1IIIKOM TOKCl14HO, qTo6hI 11CilOJih30BaTb ero B KJil1H11qecKHx 11eJIHX, HO ero IIIl1pOKO 11CilOJih3YJOT B HayqH0-11CCJie.UOBaTeJibCKOH pa6oTe ,UJIH 113yqeHHH npo11ecc11Hra rrepB11qHhIX TpattcKp11nToB PHK.
ffa611paTeJihHOCTh .ue:HCTBl1H rrpOTl1BOOIIyxoneBhIX aHTl16110Tl1KOB HeBeJI11Ka 11 06ecneq11BaeTCH 6oJiee BhICOKOtt no cpaBttett1110 c HOPMaJihHhIM11 KJieTKaM11 cKopocThJO Cl1HTe3a ,[(HK 11 PHK, a TaKxe noBhIIIIeHHOM npOHl11IaeMOCThJO KJieToqHbIX MeM6paH orryxoJieBhIX KJieTOK. B TO )l(e BpeMH 3T11 coe,UHHeHl1H TOKc11qHbl ,UJIH 6hICTpo.ueJIHIIIl1XCH ttopMaJihHhIX KJieToK opraH113Ma, TaKMx KaK cTBoJIOBhie KJieTKl1 KPOBeTBOPHOM C11CTeMhl, KJieTK11 CJil1311CTOH o60JI04Kl1 )l(eJIY,UKa 11 Kl1IIIeqH11Ka, cPOJIJI11KYJIOB BOJIOC. B nocne.utt11e ro.uh1 rrpoBO.UHTCH 11CCJie,UOBaHl1H IIO C03,UaHHJO rrperrapaTOB, 06ecrreq11BaJOII1HX ,UOCTaBKY l1Hr11611Topa TOJibKO B orryXOJieBbie KJieTKH. 3TO .UOCT11raeTCH CBH3b1BaH11eM IIl1TOTOKCWieCKHX aHTl16110Tl1KOB c 6eJIKaMl1, pe11errTOpbI K KOTOpbIM 11MeJOTCH rnaBHhIM o6pa30M Ha orryxoJieBhIX KJieTKax (cM. pa3.ueJI 15).
K npenapaTaM, ocTaHarunmaJOIIIHM peIIJI11KaIIHJO, OTHOCHT aJIKHJBl{>YJOUl,He arelITbl 11 HIO'H6HTOpbl,ll;HK-
TODOH30Mepa3bl II (O,UHOH 113 1130cPOPM TOnOl130Mepa3). IlocJie,UH11e HaJhIBaJOT IDITH611TOpaMH mpaJ,
IlOCKOJihKY ,[l,HK-rnpa3bl - cl>epMeHTbI rrpoKap110-
T11qecKHX KJieTOK, OTBeTCTBeHHhie 3a cynepcn11paJil13aII1110 ,[(HK; y 3YKaPl10TOB aHaJIOrHqttyio cPyHK-
IIHJO BhIIIOJIHHJOT L(HK-Torro1130MepaJh1. H3Becmo, qrn TpaHCKp11IIIIl1H HeKOTOPhIX reHOB B03MO)l(Ha Jil1llih rrpH orrpe.ueJieHHoM ypoBHe cyrrepcrmpa.JIH3aIIHH MaTpHIIhI. Coe.uHHeHHH, BMeIII11Ba10II111ecS1 B pa6ozy L(HK-rnpa3, MOryT HHrn611pOBaTb HJIH aKTHBHpOBaTb CHHTe3 PHK. K HHm6HTopaM mpa3 rrpHHa,UIIe)l(aT HaJil1,UHKCOBaH KHCJIOTa, HOB06HOUI1H 11 HOMepM11IIl1H.
181
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0 |
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0 |
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II |
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11 |
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.-------c |
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c---~ |
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C{i3 |
I |
C{i3 |
I |
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HC-CH |
HC-CH |
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/ |
I |
/ |
I |
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CH3 N-CH |
CH3 N-CH |
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I 3 |
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I |
3 |
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0 |
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c=o |
o=c |
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OH |
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I |
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I |
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CH2 |
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CH |
2 |
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I |
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I |
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H C-N |
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N-CH |
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3 |
I |
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I |
3 |
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c=o |
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c=o |
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0 |
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0 |
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PH2-tH |
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Ht - c,H2 |
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H2C\ |
I |
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I |
CH2 |
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0 |
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CH-N |
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N-CH |
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2 |
I |
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I |
2 |
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c~3 |
cc!:=o |
O=C |
CH |
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' |
H |
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I |
/ 3 |
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HC- |
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HC-CH |
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I |
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I |
'- |
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CH3 HN |
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HN |
CH3 |
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I |
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I |
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NH2 |
H |
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c=o |
o=c |
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I |
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I |
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~-CH-CH |
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HCCH |
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AayHoM1114111H |
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I |
I |
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I |
I |
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CH3 |
~H |
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~H |
CH3 |
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OO=:~:H,
AKTl'IHOMl'IL.\l'IHD
PMc. 4-43. CTpoeHMe «MHTepKanRTopos» - A8YHOMM4MHa M aKTMHOMM4MHa D.
B. HHrlllillTOPhI TPAHCKPHIII.J,llll
II TPAHCJUII.J,llll - AHTllliAKTEPllAJihHhIE
IIPEIIAPAThl
K 1rnrn6HTopaM MaTPl1'1HhlXCHHTe30B, OK<l3bIBa1011111M rrpOTl1B06aKTepHaJTbHOe .n:e:ikm11e, OTHOCHT Be111ecTBa, 6JIOK11pyro11111e CHHTe3 PHK HJIH 6eJIKa. B 3TY rpyrrrry BXO.UHT nrnpoKo rrpHMeHHeMbIM B KJil1HHKe pmt>aMITMUl1H, IIOJiyqaeMbIM Ha OCHOBe rrp11po,n:Horo aHTH6HOTHKa pmt>aMHUHHa. AHT116110T11K11 113 ceMe:ifcTBa pmt>aM11UHHOB HH-
rn611py10T TOJibKO 6aKTepHaJTbHYID )1,HK-3aBHCH- MYJO PHK-nOJIHMepa:Jy, CBH3hlBaHCb c ~-cy6'be.n:11-
H11ue:if <t>epMeHTa 11 rrperr.HTCTBYH HHHUI-taUHH TpaHCKpHIIUH11 (p11c. lfx rrp11MeHHlOT .n:m1 neqemra zy6epKYJie3a, TaK KaK 3rn rrperrapaTbI He BJIHHIDT Ha pa6ozy H,UepHbIX PHK-rroJIHMepaJ 3YKap110T111:1ecKHx KJieTOK. 0.n:HaKo OHH MOI)'THHrH611poBaTb CHHTe3 MllTOXOH.UPHaJibHbIX PHK, xoTH
.U03bl rrperrapaTa, rrp11 KOTOpbIX 6JIOKHpyeTCH 06paJOBaHHe MllTOXOH.UPHaJTbHbIX PHK, Bbillle Tex, 'ITO HCITOJib3YJOT B Jie'leHHHHH<t>eKUHOHHOro 3a6oJieBaHHH.
EoJiblllaH rpyrrrra attT116110T11KOB HBJIHeTcH HH-
rn611rnpaM11 TpaHCJIHUHH (p11c. TeTpauHK-
JTHHbl, 3pHTpOMHUHH, rrypOMHUHH, XJTOpaM<t>eHHKOJI 11 aM11Horn11K03H,IJ,bI. TaK, o.n:11H 113 Ha116onee H3BeCTHblX aMHHOfJIHK03H,IJ,OB CTpenTOMHil,HH HHr11611pyeT HHHUHaUHlO CHHTe3a 6eJIKa y rrpoKapH - OTOB H Bbl3bIBaeT OlllH6KH B rrpO'ITeHHH11H<t>opMau1111, 3aKo,n:11poBaHHo:if B MPHK. Ero qacTo Ha3Ha'laIOTrrptt Jie'leHHH11mpeKUHOHHblX 3a6one-
BaHHM cep.n:ua. K aHT116110T11KaM lllHpoKoro crreKTpa ).l,eMCTBHH OTHOCHT TeTpa~KJIHHbl. 0HH CBH-
3bIBaIOTCH c 30S cy6be,UHHHUeM p1160COMbl H 6JIOKHPYJOT rrp11coe.n:11HeH11e aMHHOaUHJI-TPHK B A-ueHTP p116ocoMhI, TeM caMbIM ttapyrnaa 3JIOHraumo rron11rrerrTH,IJ,Ho:if uerr11. TeTpauttKJIHHbI 3<P-
182
Ta611Ml.l8 4-5. AHTM6MOTMKM - MHrM6MTOpbt MaTPM'·IHblX6MOCMHTe30B KSK lleKapcTBeHHbte npenapaTbl
AHTH6HOTHKH |
Mexaun:JM |
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~eiicTBHH |
Uuru6urnpb1 |
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pemrnKau;uu |
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,ZJ;ayHOMIUJJiH |
BHell,p~IIOTCH ( «HHTepKarmpy10rn) Me)l()J;y napaMH OCHOBaHHH ,ll;HK H HapylliaIOT |
,ll;0Kcopy6m-1HH |
pemmKaUHIO H TPaHcKpHIIUHIO |
AKTHHOMHU,HH D |
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Memt>anaH |
ArrKHJIHpyeT ,ll;HK H HapylliaeT penJIHKaU,HIO |
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HoMepMHQHH |
IIHrn6Hpy10T ,lJ;HK-TonoH30Mepa3y TI, OTBeTcTBeHHYIO 3a cynepcnHparrH3aU,HIO |
Hoso6HOUHH |
,ll;HK, HapylliaIOT penJIHKaU,HIO H TpaHCKpHIIU,HIO |
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Uuru6nTOpb1 |
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TpaucKpHlll.\HH |
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P11qJaMHll,HHbl |
Cml3bIBaIOTCH c 6aKTepHanhHOi1 PHK-rrorrHMepa3oii: H rrperrHTCTBYIOT Ha'l.arry |
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TpaHCKpHIIll,HH |
Huru6nTOpbI |
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TpaHCJIH).\HH |
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TeTpaUHKJIHHhI |
l1Hrn6Hpy10T 3JIOHraU,HIO: CBH3bIBaIOTCH c 30S cy6bell,HHHU,ei1 p116oc0Mbl H |
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6rroK11py10T rrp11coeD,11HeH11e aa-TPHK B A-QeHTP |
JleBOMHU,eTlrn |
IlpHCOell,HHHeTCH K sos cy6bell,HHHU,e p1160COMbl H HHrH6HpyeT |
|
rrerrTHll,HJITPaHccjlepa3HYIO aKTHBHOCTb |
3pHTpOMHll,HH |
IlpHcoeD,HHHeTcH K SOS cy6bell,HHHQe pH6ocOMhI H HHrn6HpyeT TPaHCJIOKaU,HIO |
CTperrTOMHU,HH |
llHrH6HpyeT HHHU,Hau,HIO TpaHCJIHU,HH. CBH3bIBaeTCH c 30S cy6bell,HHHU,eii |
|
pH6ocOMhI, BhI3hlBaeT onm6K11 B rrpo'l.TeHHH11HcjJOpMau,H11, 3aKOD,Hposattttoi1 B MPHK |
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cpeKTl1BHbl B OTHOIIIemm B036y.n:11TeJieM MHOfl1X 6oJie3HeH. JleBOMHU,eTHH (XJiopaMcpeHl1KOJI) TaIOKe OTHOCSIT K am116ttOT11KaM llil1POKOro cneKTPa .n:ei:\:- CTBIDI. OH 11Hr11611pyeT Cl1HTe3 6e11Ka 3a cqfa np11coe,IJ,11Hemrn K SOS cy6be,IJ,ttH1111,e p116ocoMhI, no-
.n:aruurn nenn1.n:MJ1TPaHccpepa3tty10 aKTMBHOCTh.
IlellHUHJJJHIHhI H u,efi>aJIOCDOpHHbl OTHOC51T K rpyn-
ne P-naKTaMHhIX aHTtt6110T11KoB, rrpo.n:yIJ,11pyeMhIX IIJieceHbIO rmaMMa Penicillum. B CTPYKTYPe 3Tl1X
Moneeyn npWCYTCTByeT peam110HH0-cnoco6Hoe P- JiaKTaMttoe KOJibIJ,O, Bbl3blBaIOlllee HHr116ttpOBaH11e Cl1HTe3a KJieTOqHbIX CTeHOK y rpaMOTpHIJ,aTeJihHhIX Ml1KpoopraH113MOB. .ll,ettCTBHe 3Tl1X aHTl16110T11KOB HarrpaBJieHo Ha ¢epMeHT, 06ecrreq11Bmoll1HM o6pa30BaH11e rrorrepe'l.HhIXCB513ei:\: B cTpyKrype 6enKOB KJieTO'l.HOM cTemrn 6aKTeptttt. Heo6paT11Moe l1HrH611poBaH11e aKTl1BHOCTH 3TOfO cpepMeHTa Be-
.n:fa K o6pa30BaHl1IO l13MeHeHHblX KJieTOl.J.HhIX CTeHOK 11 m:6en11 6aKTepttii B rrpo11,ecce pa3MHO)J(e- Hl151.
Ha.n:o CKa3aTh, 'ITOnperrapaThI aHTtt6aKTep11aJihHOM rpyrrIIbl OTJIHqaJOTC51 BbICOKOH H3611paTeJihHO-
NH
I/ 0
P111cflaM1111.1111H B(R1 = H; R2 = O-CH2- COOH)
+/\
P111cflaMm11.1111H (R1 =CH= N N-CH3 ; R2 = OH)
\ _ /
PMC. 4-44. AHTM6MOTMKM M3 ceMetliCTBa pMcj>aMM~MHOB.
183