catabolismul pirimidinice1

7/25/2019 CATABOLISMUL PIRIMIDINICE1

http://slidepdf.com/reader/full/catabolismul-pirimidinice1 1/19

UNIVERSITATEA TEHNICA DIN CLUJ NAPOCA CENTRUL UNIVERSITAR NOBAIA MARE

FACULTATEA DE ȘTIINȚEDEPARTAMENTUL DE CHIMIE ȘI BIOLOGIE

Specializarea BIOCHIMIE APLICAT!

Pr"#e$"rDr% L&cia Mi'aie$c&

MRe+eca ,Ra

CATABOLISMUL BAZELOR PIRIMIDINI



•CUPRINS:

• ASPECTE GENERALE

• CATABOLISMUL BAZELOR PIRIMIDINICE

• BIOSINTEZA DE NOVO A NUCLEOTIDELOR PIRIMIDIN

• ASPECTE DE PATOLOGIE DIN METAB

NUCLEOTIDELOR PIRIMIDINICE



Sinteza nucleotidelor pirimidice

2 căi:• Sinteza de novo. Sinteza nucleotidelor începe de la precur

metabolici: aminoacizi, ribozo-5-fosfat, CO2 , şi 1C .

• Reciclare. Sinteza nucleotidelor prin reciclarea bazelor şi nucleotidelor eliberate prin scindarea acizilor nucleici.

• N&cle"(i*ele piri/i*i)ice $er-e$c la $i)(eza al("rc"/p&$i /acr"er0ici1 *")"ri *e 0l&ci*e i) $i)(ez0lic"0e)&l&i ,UDP20l&c"za. $a& pe)(r& $i)(eza0lic"pr"(ei)el"r ,UDP20alac("za.%



Sinteza de novo

• L"calizare

Ci("$"lic3 4) 5ca(1 i)(e$(i) $&+6ire 7i (i/&$• Carac(eri$(ici

a% P&ri)ele $&)( $i)(e(iza(e #"l"$i)* ri+"z"2#"$#a(&l/a(erial *e 4)cep&(9

+% PRPP,82#"$#"ri+"zil2:2pir"#"$#a(. e$(e *")"r&l acP%

c% AMP 7i GMP $&)( (ra)$#"r/a(e &l(eri"r 4) IMP,I)"M")"#"$#a(.%



• Cale /ai $c&r(a *ec<( pe)(r& p&ri)e• Spre *e"$e+ire *e +i"$i)(eza p&ri)e

e$(e $i)(e(iza( i)el&l piri/i*i)ic1 ap"la ri+"z"2P

• N&/ai = prec&r$"ri ,a$par(a( $i 0l&pl&$ HCO>2. c")(ri+&ie la i)el&l c& ?

• Nece$i(3 ? e(ape ,i) l"c *e :: pe)(r& • Pr"*&$&l e$(e UMP ,&ri*i) /")"#"$#a(



S&r$a +azel"r piri/i*i)ice



• E@peri/e)(e c& /areri ra*i"ac(i-i a& ara(a( ca a("/ii N,:C,8. $i C,?. ai cicl&l&i piri/i*i)ic pr"-i) *i) $c'ele(&l aci*&la$par(ic1 a("/&l ,C. pr"-i)e *i) CO= $i a("/&l N,>. e$(e prela 0l&(a/i)a%

• :% Si)(eza car+a/"il #"$#a(&l&i e$(e pri/a reac(ie a +piri/i*i)el"r1 e)zi/a 5i)* car+a2/"il #"$#a( $i)(e(aza II e@ci("$"l% U)a *i) cele *"&a /"lec&le *e ATP care $e c"reac(ie #&r)izeaza " 0r&pare #"$#a( iar cealal(a c")(ri+&ie c)ece$ara la car+"@ilarea az"(&l&i a/i)ic1 #ara i/plicarea

c"e)2zi/a (ipica a)0aa(a i) reac(iile *e car+"@ilare la acar+")% A/ -az&( la cicl&l &re"0e)e(ic ca e)zi/a car+a/"il #"$#a( $i)(e(aza I1 ca(alizeaza car+"@ilarea $i #"&)&i a("/ *e az"( *i) a/")iac $i e$(e l"caliza(a i) /i("c"pr"cari"(e e@i$(a " $i)0&ra $i)(e(aza care ca(alizeaza a//e(a+"lice ,piri/i*i)"0e2)eza $i &re"0e)eza.%



=% Si)(eza car+a/"il a$par(a(&l&i e$(e ca(aliza(a *e a$par(a( (ra)$car+a/"ila

• F"r/area *i'i*r""r"(a(&l&i are l"c pri) i)c'i2*erea cicl&l&i ca(aliza(a *e *iPri/ele > e)zi/e1 $i)(e(aza II1 ATC $i *i'i*r""r"(aza #ac par(e *i)(r2" $i)0(ri#&)c(i")ala la e&cari"(e% Acea$(a pr"(ei)a )&/i(a CAD1 c")$(a *i)

p"lipep(i*ice i*e)(ice a-a)* /a$e /"lec&lare *e => Da1 5ecare c")(ce)(ri ac(i-i ai e)zi/el"r ara(a(e% I)(e0rarea ace$("r e)zi/e i)(r2&/&l(ie)zi/a(ic e$(e *e a$(ep(a( *a("ri(a carac(er&l&i rela(i- *ez"r20a)iza( a

• % O@i*area *i'i*r""r"(a(&l&i e$(e " reac(ie re-er$i+ila ca(aliza(a *e **e'i*r"20e)aza1 e)zi/a e&cari"(ica c")(i)a)* FMN $i #er )e'e/i)ic 5i)*/e/+ra)a i)(er)a /i("c")*riala% C'i)")e i)(er/e*iaza (ra)$#er&l a'i*r"0e)% Acea$(a *e'i*r"0e)aza e$(e $i)0&ra e)zi/a /i("c")*riala ("a

e)zi/e ale piri/i*i)"0e)ezei 5i)* ci("$"lare%• 8% Pla$area *i'i*r""r"(a(&l&i pe #"$#"ri+"za are l"c c& i/plicarea

/acr"er0ic 82#"$#"ri+"$il2pir"#"$#a( ,PRPP. rez&l(a)* "r"(i*i)28;2/")"#"Reac(ia e$(e ca(aliza(a *e "r"(a( #"$#"ril (ra)$#eraza care p"a(e ac(i")a $*e $al-are pe)(r& +aze piri/i*i)ice ca &racil&l $i ci("zi)a pe care le (r)&cle"(i*ele /")"#"$#"rice c"re$p&)za("are%



?% Decar+"@ilarea OMP



Ca(a+"li$/&l )&cle"(i*el"r piri/i*i)• Se*i&l ca(a+"li$/&l&i piri/i*i)el"r e$(e 5ca(&l% Pr"*

ca(a+"li$/ $&)( 0aze &$"r $"l&+ile i) apa,NH>1 CO=.c"/p&$i &$"r /e(a+"liza+ili%

• Cel&lele a)i/alel"r *e0ra*eaza )&cle"(i*ele piri/i*i)i$(area *e +aza ,&racil1 (i/i)a.% Ace$(e (ra)$#"r/ari a& l"c*e *e#"$#"rilare,'i*r"liza. $&+ ac(i&)ea )&cle"(i*azel"r $i *cli-a a le0a(&rii N20lic"zi*ice $&+ ac(i&)ea &)ei #"$#"ri2laze

• N&cle"+azele $&)( re*&$e i) 'epa("ci(e iar *i'i*r")&cle"

*ecicliza(e $i 'i*r"li2za(e rez&l(a)* 2Ala $a& 2a/i)"iz"+*e NH> $i CO=% Pri) &r/are1 $pre *e"$e+ire *e ca(a+"l)&cle"(i*el"r1 pr"*&$ii 5)ali ai piri/i*i)2)&cle"(i*el"r $&)&$"r $"l&+ile i) apa%

• A$(#el1 i) c")*i(iile &)ei $&prapr"*&c(ii *e piri/i*i)e )&$e/)e cli)ice *e"arece pr"*&$ii *e *e0ra*are ai ace$

ac&/&leaza ca aci*&l &ric $i &ra(ii% Hiperpr"*&c(ia *e PRPcre$(erea ace$("r c"/ &$i% A/i)"acizii rez&l(a(i $&)( r



• Bazele piri/i*i)ice $&)( &racil&l1 ci("zi)a1 7i (i/• Rez&l(3 aci*&l 2&rei*"2pr"pi")ic 7i 2&rei*"2iz"

care $e (ra)$#"r/3 4) 2a/i)"2iz"+&(iric•

Aci*&l 2&rei*"2pr"pi")ic (rece 4) 2ala)i)3• 2ala)i)a 7i aci*&l 2a/i)"2iz"+&(iric ,BAIB. $&#e

reac6ie *e (ra)$a/i)are 7i $e #"r/eaz3 $e/ial*ec"re$p&)z3("are ,/al")ic3 7i /e(il2/al")ic3.

• Eli/i)area pri) &ri)3 a BAIB e$(e cre$c&(3 7i 4) le

7i ira*ieri c& raze • Eli/i)area cre$c&(3 *e BAIB $e 4)(<l)e7(e la 82:

e&r"pe)i 7i la apr"@i/a(i- *i) "rie)(ali1 #3r3ca&za " $&#eri)63 7i #3r3 a $e c&)"a7(e e@plica6ia



BIOSINTEKA DE NOVO A NUCLEOTIDELOR PURINICE

• Se $i)(e(izeaz3 pe $ea/a aci*&l&i i)"zilic ,IMP.•

Are l"c 4) ci("$"l1 pri)(r2" $&cce$i&)e *e : reac6ie)zi/a(ice• He(er"cicl&l +azei e$(e c")$(r&i( *irec( pe ri+"z"2#"$#a(

• A("/ii *i) )&cle&l p&ri)ic pr"-i) *i) c"/p&7i $i/

Gl1 Gl)1 A$p1 CO= 7i #ra0/e)(e C:2ac(i-e 4)c3rpe THF• Si)(eza are l"c /ai ale$ 4) 5ca(



BIOSINTEKA DE NOVO A NUCLEOTIDELOR PIRIMIDINICE

•

S&r$a a("/il"r *i) cicl&l piri/i*i)ic A$p1 Gl)1 CO



RECICLAREA BAKELOR PIRIMIDINICE

•

Uracil&l p"a(e 5 recicla(• E)zi/a "r"(a(2#"$#"ri+"zil (ra)$#erazei ,OPRT.

• Pri) ac6i&)ea &ri*i)2#"$#"rilazei $e #"r/eaz3 &ri*



Reciclarea piri/i*i)el"r



PATOLOGIA METABOLISMULUI PIRIMIDINELOR

:% Aci*&rie "r"(ic3 ere*i(ar3• E$(e *e *"&3 #el&ri 2 *e (ip I 2 *e (ip II• Cli)ic 2 lip$a *e cre7(ere a )"il"r )3$c&6i

2 le&c"pe)ie

2 a)e/ie /e0al"+la$(ic3• Eli/i)area &ri)ar3 cre$c&(3 *e aci* "r"(ic 7i apa

li(iazei re)ale• A*/i)i$(rarea *e )&cle"(i*e 7i )&cle"$i*e p&ri)i

la a/eli"rarea +"lii



=% A)e/ia 'e/"li(ic3 ere*i(ar3• De5cie)63 *e piri/i*i)282)&cle"(i*az3•

Ac&/&l3ri /a$i-e *e )&cle"(i*e piri/i*i)i'i*r"liza ARN• I)'i+area ace$(ei e)zi/e 4) i)("@ica6iile c&e$(e &)a *i) ca&zele a)e/iei carac(eri$(icace$(&i (ip *e i)("@ica6ii

catabolismul pirimidinice1

Documents