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Curs biofarmacie

Jun 04, 2018

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    LUCIANA DOBJANSCHI

    BIOCHIMIE FARMACEUTIC

    EDITURA UNIVERSITII DIN ORADEA

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    2007

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    Biochimie farmaceutic

    Refereni tiinifici:

    Conf.dr. !re"n "ri"n"Conf.dr. ic#e Oti#i"

    EDITURA UNIVERSITII DIN ORADEA ESTE ACREDITAT DECNCSIS

    CONFORM POIIEI !"#$

    Ti%ar&METROPO'IS SR'

    Ora(ea) *tr$ Nico+ae ,i-a .r$/!Te+$& 012# 3"4 !50) 0133 3"4 !50

    Te+$6 Fa7& 024# "12 5"0e8mai+& metro%o+i*9r(*+i.:$ro

    $

    Descrierea CIP a Bibliotecii Naioale a Ro!"ieiDOBJANSCHI# LUCIANA Bioc$i!ie %ar!ace&tic'% Do&'"n(c)i *!ci"n". +Or"de" : Edit!r" Uni,er(it-ii din Or"de" 2007

    /iior. IS/N 17+17$+731+422+

    377.5:653

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    'ucia.a Do;

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    Biochimie farmaceutic

    4II(7( Utili+area sc$elet&l&i )e ato!i )e carbo ai a!ioaci+ilor4II(8( Biosite+a a!ioaci+ilor4III( Metabolis!&l &cleoti)elor

    4I/( Metabolis!&l $e!o,lobiei4/( Biblio,ra%ie

    3

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    'ucia.a Do; cercet-ri ce "! de8on(tr"t c- "ce(te roe8e f!nd"8ent"#eot fi eficient "&ord"te rin 8etode &ioc)i8ice.

    ?ntr+"de,-r (!cce(!# &ioc)i8iei

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    Biochimie farmaceutic

    "nor"nic-. D"c- &io#oi" e(te c)i8ie e" e(te !n fe# de s&*rac$i!iec"re inc#!de d"r

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    'ucia.a Do;

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    Biochimie farmaceutic

    T"&e#!# 2. ;rinci"#e#e &io8o#ec!#e din or"ni(8!# !8"n

    /io8o#ec!#" Unit-i (tr!c!r"#e !nciiADN de9o=iri&on!c#eotide "teri"# eneticARN ri&on!c#eotide ode# entr!

    (inte9" roteine#orroteine "8ino"ci9i !ncii 8!#ti#e#!cide 8ono9")"ride Re9er,- de enerie#iide Aci9i r"i i "#i

    co8oneni!ncii 8!#ti#e

    Co!*oeii !ieralire9eni

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    'ucia.a Do;

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    Biochimie farmaceutic

    T"&e#!# $. Di(tri&!i" c"tioni#or intr"+ i e=tr"ce#!#"r

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    'ucia.a Do;

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    Biochimie farmaceutic

    /"9e#e iri8idinice re9int- !n n!c#e! de &"9- n!8it iri8idin" de#" c"re deri,- $ &"9e iri8idinice c"re int-

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    'ucia.a Do; ri&o9" 2 > de9o=i > D > ri&o9"

    54

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    Biochimie farmaceutic

    ;rin "t""re" !nei ento9e #" &"9" "9ot"t- re9!#t- on!c#eo9id- c"re de9o=i"deno9in" "deno9in"

    ;rin "t""re" !nei 8o#ec!#e de "cid fo(foric #" (tr!ct!r" !nein!c#eo9ide (e for8e"9- !n n!c#eotid.

    N

    N

    N

    N

    N=2

    2=

    O==

    O=

    C

    =

    =

    =

    OP

    O=

    O

    O

    PO

    O

    O=

    P

    O=

    O

    =O

    AMP

    ADP

    ATP

    53

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    'ucia.a Do; ri&o9".

    2= O==

    O=

    C

    =

    =

    =

    OP

    O=

    O

    =O;a>a a>otat?

    de9o=iri&on!c#eotid

    2=O

    ==

    O=

    C

    =

    O=

    =

    OP

    O=

    O

    =O;a>a a>otat?

    ri&on!c#eotid

    56

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    Biochimie farmaceutic

    N!c#eo9idtrifo(f"ii re9int- o (erie de f!ncii i8ort"nte.AT; e(te !n tr"n(ortor de r!-ri fo(f"t i irofo(f"t !#!i e(te refo(fori#"t #"AT;

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    'ucia.a Do; !# e(te co8!( din #"n!ri deri&on!c#eotide. Aci9ii de9o=iri&on!c#eici i "ci9ii ri&on!c#eicire9int- o (erie de rorit-i fi9ice i c)i8ice co88!ne )idro=i# " !r8-to"rei n!c#eotide.

    5

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    Biochimie farmaceutic

    O

    C

    =

    = =

    O

    =

    =

    =2

    ;a>? a>otat?

    4@

    /@

    P O=O

    O

    C=2O

    =

    ==

    =

    ;a>? a>otat?

    O

    P O=O

    O

    4@

    /@

    ADN

    51

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    'ucia.a Do;? a>otat?

    4@

    /@

    P O=O

    O

    C=2O

    =

    ==

    O=

    ;a>? a>otat?

    O

    P O=O

    O

    4@

    /@

    ARN

    A(tfe# c"ten" rinci"#- " ADN i ARN con(t-

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    Biochimie farmaceutic

    o#ec!#e#e de ADN din diferite ce#!#e i ,ir!(!ri (edeo(e&e(c rin r"ort!# dintre ce#e 4 ti!ri de 8ono8eri n!c#eotidicirin (ec,en" n!c#eotide#or i rin 8"(" 8o#ec!#"r-. ;e #n- ce#e 4

    ti!ri de &"9e 8"'ore

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    'ucia.a Do;10 de n!c#eotide. iec"re dintre cei 20 de "8ino"ci9i din roteine "re

    ce# !in !n ARNt coer(!n9-tor i"r !nii "! c)i"r 8"i 8!#i ARNt.De e=e8#!: citidi# >"deni# CCAB. r!"re" 3H>)idro=i# " "cid!#!i "deni#ic ter8in"# e(te

    #e"t- de r!"re" $

    H

    >)idro=i# " "cid!#!i citidi#ic recedent rint+o!nte fo(fodie(teric-. r!"re" )idro=i# #i&er- din "cid!# "deni#icter8in"# e(te "ci#"t- en9i8"tic c! M+"8ino"cid!# (ecific for8nd"8ino"ci# >ARNt. Ace(t "8ino"cid e(te tr"n(fer"t en9i8"tic #"c"-t!# #"n!#!i o#ietidic

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    Biochimie farmaceutic

    dect ce#!#e#e roc"riote e=i(t- 4 ti!ri de ARNr: 3S 7S 5S i 2S.Dei ARNr rere9int- o 8"re "rte din ARN ce#!#"r tot"# f!nci" #!i roteine c! (tr!ct!ri i f!ncii &io#oice fo"rteco8#e=eL ri&o9o8ii i ,ir!(!ri#e (!nt ce#e 8"i c!no(c!te. Ce#e 8"ico8#e=e (i(te8e "cid n!c#eic > rotein- (!nt ro&"&i# cro8o9o8iidin ce#!#e#e e!c"riote.

    Ri&o9o8ii (!nt "rtic!#e ri&on!c#eoroteice c"re (e -(e(c

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    'ucia.a Do;tr"n(8i-tor.A8ino"ci9ii (!nt rec!r(orii !nei ,"rit-i de &io8o#ec!#e dee=e8#!: )itidin" entr! )i(t"8in-B. Unii "8in"ci9i (!nt8et"&o#i9"i i !ti#i9"i entr! rod!cere" de #!co9-#!coneoene9-B. Deo"rece n! e=i(t- re9er,e de "8ino"ci9i c!e=cei" ce#or i8#ic"i

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    Biochimie farmaceutic

    R C= COO

    N=/

    8

    ?n toi M+ "8ino"ci9ii c! e=cei" #icinei c"r&on!# M e(te otic"cti,. I9o8erii o(i&i#i ""rin (eriei D ("! *. S+" con(t"t"t c- toii9o8erii e=i(teni

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    'ucia.a Do;

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    Biochimie farmaceutic

    + "8ino"ci9i c! do!- r!-ri &"9ice

    =2N C=2 C=2 C=2 C=2 C= COO=

    N=2

    #i(in" #(B

    =2N C N= C=2 C=2

    N=

    C=2 C= COO=

    N=2"rinin" "rB

    N N=

    C=2 C= COO=

    N=2

    )i(tidin" )i(B

    + "8ino"ci9i "ro8"tici

    C=2 C= COO=

    N=2

    feni#"#"nin" )eB

    C=2 C= COO=

    N=2

    =O

    tiro9in" trB

    27

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    'ucia.a Do; c"re "!

    r"dic"#!# o#"r d"r #i(it de ("rcin- e#ectric- #" 7.+ "8ino"ci9i )idrofi#i c! c"r"cter "cid: A( #! Tr > c"re (!nt

    "8ino"ci9i "8ino"ci9i

    c"re #" fi9io#oic (!nt

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    Biochimie farmaceutic

    + "cid!# K+ "8ino&!tiric A/AB e(te !n 8edi"tor c)i8ic ner,o(+ $4 > dio=ifeni#"#"nin" DO;AB e(te rec!r(or "# "dren"#inei+ "cid!# + "8ino&en9oic intr-

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    'ucia.a Do;

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    Biochimie farmaceutic

    =OOC C=

    N=2

    C=2 C=2 CO N= C= CO

    C=2

    N= C=2 COO=

    S=

    #!t"tion!# (e

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    'ucia.a Do;ima (e co.Ger*i

    A.-iote.*i.a II

    octa%e%ti(

    ami.o%e%ti(a>a

    A.-iote.*i.a III

    he%ta%eti(

    %rotei.a %+a*matic?ca%to%ri+

    Anioten(ine#e "cione"9- "(!r" ,"(e#or 8"i inten( e "rtere(ti8!#nd (ecrei" de "#do(teron i e#i&er"re" de ro(t"#"ndine.Anioten(in" II e(te (ocotit- ce# 8"i !ternic "ent re(or re(ent

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    Biochimie farmaceutic

    Un "#t e=e8#! de o#ietide n"t!r"#e e(te rere9ent"t de,"(ore(in- i o=itocin- c"re (!nt etide cic#ice "#c-t!ite n!8"i din"8ino"ci9i. Ace(te do!- o#ietide "! o (tr!ct!r- fo"rte "roi"t-

    fiind "#c-t!ite din 1 re(t!ri de "8ino"ci9i d"r re9int- f!nciifi9io#oice diferite. V"(ore(in" "re efect "ntidi!retic i"r o=itocin""cione"9- "(!r" 8!(c!#"t!rii netede " !ter!#!i rod!cndcontr"ci" !ter!#!i. O=itocin" (ti8!#e"9- i contr"ci" 8!(c!#"t!riidin '!r!# "#,eo#e#or 8"8"re deter8innd "(tfe# e#i8in"re" #"te#!idin c"n"#e#e #"ndei 8"8"re ",nd "ci!ne #"ct"o-.

    $$

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    'ucia.a Do;

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    Biochimie farmaceutic

    "(" 8o#ec!#"r- " roteine#or (e o"te deter8in" rin 8etodefi9ice i o"te fi c!rin(- rotein" din "#&!!# de o!+ c"9ein" > rotein" din #"te+ feritin" > rotein" de deo9it"re " e rotein" din r!

    $. ;roteine de tr"n(ortE=e8#!:

    + )e8o#o&in" > rotein" ce tr"n(ort- o=ien!# rotein" ce tr"n(ort- "ci9ii r"i roteine#e din ci#i i f#"e#i.?n 8!c)i "ctin" i 8io9in" (!nt "e9"te

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    'ucia.a Do;

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    Biochimie farmaceutic

    + e#"(tin"+ 8!coroteine#e.

    Aticor*ii -i r's*&s&l i!&( S*eci%icitatea )e s*ecie a*roteielor.

    Anticorii ("! i8!no#o&!#ine#e "! o i8ort"n- fo"rte 8"re

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    'ucia.a Do;

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    Biochimie farmaceutic

    i. 2. ;rinci"#e#e ti!ri de (tr!ct!ri "#e roteine#or

    Str!ct!ri#e roteice (!nt (t"&i#i9"te de do!- ti!ri de #e-t!ri!ternice:legtura peptidic i puntea disulfidic rec!8 i de trei ti!ri de#e-t!ri (#"&e.*e-t!r" di(!#fidic- (e (t"&i#ete

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    'ucia.a Do; "8inic- " #i9inei.

    Un ro# (e8nific"ti,

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    Biochimie farmaceutic

    + identific"re" "8ino"ci9i#or co8oneni rin difr"cie c! r"9e @ i(ectro(coie

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    'ucia.a Do;

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    Biochimie farmaceutic

    Con(ecine#e for8-rii "ce(t!i (i(te8 !ternic con'!"t (!ntco#"n"rit"te" ce#or 4 "to8i cee" ce re(!!ne i8o(i&i#i"te" rotiriii e=i(tenei for8e#or ci( i tr"n(. S+" o&(er,"t c- i9o8er!# tr"n( e(te

    f",ori9"t deo"rece e(te 8"i (-r"c

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    Biochimie farmaceutic

    i!r" nr.3. Str!c!r" de fo"ie #i"t-.

    A8ino"ci9i 8ici: # "#" ","nt"'e"9- fo"i" #i"t- i"r cei c!r"dic"# 8"re ("! c! ("rcin- (tn'ene(c "r"n'"8ent!#.

    C" i 8ode#!# de M+)e#i= (tr!ct!r" P (e

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    Biochimie farmaceutic

    3. Confor8"i" de "n("8! " #"n!#!i o#ietidic e(te ""rent"cee"i #" 8io#o&in" t!t!ror (ecii#or (ecii#or (t!di"te dei e#edifer- o"rec!8

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    'ucia.a Do;

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    Biochimie farmaceutic

    ?n 8o#ec!#" )e8o#o&inei r-8ne o c",it"te cent"#- 8-rinit- der!-ri c! r"dic"# R o#"re.

    i!r" nr.. or8"re" )e8o#o&inei

    Deat&rarea *roteielorDen"t!r"re" roteine#or rere9int- ert!r&"re" (tr!ct!rii #or

    n"ti,e

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    'ucia.a Do;

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    Biochimie farmaceutic

    /( /ITAMINE

    Vit"8ine#e (!nt &io8o#ec!#e indi(en("&i#e ,ie!ito"re#or

    entr! cretere"

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    'ucia.a Do;

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    Biochimie farmaceutic

    /(0( /ita!iele li*osol&bile

    Vit"8ine#e #io(o#!&i#e (!nt 8o#ec!#e "o#"re deri,"te din

    i9oren. E#e (!nt re#"ti, (t"&i#e #" te8er"t!r" oer"ii#or c!#in"red"r !or in"cti,"te de r"di"ii#e UV i (!&(t"ne#e o=id"nte.Die(ti" i "&(or&i" #or dec!re

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    'ucia.a Do; c"roten

    ?n 8!co"(" inte(tin"#- P+ c"roten!# (!fer- o (cind"reo=id"ti,- " #e-t!rii d!e din o9ii" 53 roce( en98"ticB a

    ,it"8in" A5retin"#!#B

    Tot

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    Biochimie farmaceutic

    C=O

    C=2O=

    a+coo+

    (ehi(ro-e.a>a

    retino#

    + o=id"re" r!-rii "#de)idice #" "cid c"r&o=i#ic

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    'ucia.a Do;

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    Biochimie farmaceutic

    Retial&lRetin"#!# "rtici- direct

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    'ucia.a Do;omeri>are

    +umi.a

    !!8ci* reti.a+

    C= N=

    o%*i.a

    a++ tra.* reti.a+

    ;rin i9o8eri9"re (e (c)i8&- eo8etri" (tr!ct!rii o#ienice "rodo(inei "re #oc o de#"("re " #e-t!rii "#di8inice c! 3A0

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    Biochimie farmaceutic

    ;roce(!# de e=cit"re ,i9!"#-.Carea )e .iat!ia A

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    'ucia.a Do;

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    Biochimie farmaceutic

    S&rsa e)o,e' )e .ita!ia D

    *i.te>a e.(o-e.a a+ime.te

    co+e*tero+

    mucoa*a i.te*ti.a+a

    (ehi(roco+e*tro+1

    +umi.a

    =O

    co+eca+cifero+

    ;rin "ci!ne" r"di"ii#or UV 7+de)idroco#e(tero#!# for8"t

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    'ucia.a Do;a

    hi(ro7ica+cifero+24

    ca+cifero+!)24 ca+cifero+2")24ca+citrio+

    ca+cifero+!)2")24

    O=

    O=

    =O

    ca+citrio+

    62

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    Biochimie farmaceutic

    Rol&l bioc$i!ic al .ita!iei D

    Vit"8in" D "#-t!ri de )or8on!# "r"tiroidi"n inter,ine

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    'ucia.a Do;

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    Biochimie farmaceutic

    /ita!ia E ;toco%eroliia

    M-2

    / C=2C=O=C=2

    =/C

    =/C N

    N N=

    N

    O

    O

    O P O P O C=2

    O= O=

    O OO

    N

    N

    N

    N

    N=2

    O==O

    AD

    Dintre "ce(te do!- for8e AD rere9int- 0 N > 20i"r ri&of#",in" #i&er- r-8ne

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    Biochimie farmaceutic

    Rol bioc$i!ic

    A8&e#e f#",in+n!c#eotide N ADB (!nt coen9i8e c"re

    f"c "rte din (i(te8e en9i8"tice i8#ic"te

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    Biochimie farmaceutic

    N

    CON=2

    O

    O=O=

    C=2 O P O P

    O

    O=

    O

    O

    O=

    C=2

    O

    N

    N N

    N

    O=O R

    N=2

    R : NAD ;O$2 NAD;

    ?n ce#!#e#e "ni8"#e NADFe(te re9ent

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    Biochimie farmaceutic

    /ita!ia B8

    Vit"8in" /6 n!8it- i irido=in" ("! "der8in" ""re (!&

    trei for8e &io#oic "cti,e intercon,erti&i#e. Vit"8in" /6(e -(ete

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    'ucia.a Do;a

    ATP

    ADPN

    C=O

    C=2=O

    =/C

    P

    O

    O=

    O=

    O=

    O=P

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    Biochimie farmaceutic

    C

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    Biochimie farmaceutic

    4I(1( Metabolis!&l aci+ilor ,ra-i sat&rai

    Catabolis!&l aci+ilor ,ra-i

    Aci9ii r"i (e der"de"9- rin ced"re" (!cce(i,- " !norfr"8ente de 2 "to8i de C

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    'ucia.a Do;+is' ;> o3i)areaito+

    ;rin fo(fori#"re" r!-ri#or O din ino9ito#

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    Biochimie farmaceutic

    car(io+i%i.a

    fo*fati(i+-+icero+

    fo*fati(i+-+icero+fo*fat

    C=2 OCO R!

    O=O=

    O P O

    O

    C=2 C= C=2 O P O

    O

    C=2

    C= OCO R2

    C=2

    R2 COO C=

    R! COO C=2

    O=

    CMPCDPL(iaci+-+icero+

    O=

    R! COO C=2

    C=R2 COO

    C=2 O P OO

    C=2 C= C=2 O=

    O=

    fo*fati(i+-+icero+fo*fata>a

    =/PO"=2OO=

    O=C=2 O P

    O

    O=

    O P O

    O

    C=2

    C= O=

    C=2

    R2 COO C=

    R! COO C=2

    CMP

    O=

    C=2 O P O=

    OC= O=

    O=C=2

    O=O=

    O P O

    O

    P citi(i+

    OR2COO C=

    C=2

    C=2 OCO R!

    1( Biosite+a ,licerol%os%oli*i)elor *lec") )e la 0#1>)iacil,licerol

    ;e "ce"(t- c"#e (e (inteti9e"9- #ecitin" i cef"#in"

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    Biochimie farmaceutic

    N

    N

    N

    N=2

    O

    O=

    C=2 S C=/

    O=

    C=22

    C= N=2

    COO=

    C=2 OCOR!

    C= OCOR2

    C=2 O P

    O

    O C=2 C=2 N=2

    O=

    /

    /

    COO=

    C= N=2

    C=22

    O=

    N

    N

    N

    N=2

    O

    O=

    C=2 S

    O=

    O C=2 C=2 NC=//P

    O

    OC=2

    OCOR2C=

    C=2 OCOR!

    SAM

    +eciti.a

    SA=

    Biosite+a %os%ati)ilseriei

    ?n e(!t!ri#e "ni8"#e (inte9" fo(f"tidi#(erinei con(t-

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    'ucia.a Do;a

    A!

    D

    C

    A2

    o(fo#i"9" A5 (cinde"9- #e-t!r" e(ter din o9ii" 5 "fo(fo#iidei e#i&ernd "cid!# r"(. o(fo#i"9" A2 "cione"9- "(!r"#e-t!rii e(ter din o9ii" 2 e#i&ernd "cid!# r"( ne("t!r"t. ;rin

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    Biochimie farmaceutic

    o(fo#i"9" A2c"re (cinde"9- "cid!# r"( ne("t!r"t din o9ii"2 f!rni9e"9- "(tfe# "ci9i r"i ne("t!r"i entr! (inte9"ro(t"#"ndine#or tro8&o="ni#or i #e!cotriene#or. ?n "ncre"tit"

    "c!t- fo(fo#i"9" A2 trece

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    'ucia.a Do;i.a

    A#te e=e8#e de (fino#iide: Sfino8ie#in" cere&ri9ide#e (!#f"tide#e i "n#io9ide#e.

    De,ra)area s%i,oli*i)elor

    Sfino#iide#e (!nt der"d"te de c-tre (fino8ie#in"9- oen9i8- c"re

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    Biochimie farmaceutic

    4I(9( Metabolis!&l colesterol&l&i

    Co#e(tero#!# e(te !n (tero# 8"'or

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    'ucia.a Do;)idro=iP+8eti#+

    #!t"ri#+CoA+(intet"9ei +CoA+(intet"9"B i for8e"9- +CoA. "i de"rte r!"re" c"r&o=i#ic- #e"t- de CoA e(te red!(- #"r!"re )idro=i#ic- c! e#i8in"re de CoA. Re"ci" "re #oc a

    =OOC C=2 C

    O=

    C=/

    C=2 COSCoA

    C

    O=

    C=/

    C=2 COSCoA=OOC C=2 2NADP= 2=

    =MLCoA re(ucta>a

    =OOC C=2 C

    O=

    C=/

    C=2 C=2 O= 2NADP

    CoAS=

    51

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    Biochimie farmaceutic

    1( Tras%or!area aci)&l&i !e.aloic ? sc&aleAcid!# 8e,"#onic (e fo(fori#e"9-

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    'ucia.a Do;a

    C

    C=/

    C==/CC=2

    C=2

    C

    C=/

    C=

    C=2 O P O P O=

    O O

    O= O=

    -era.i+%irofo*fat

    O=O=

    C=2 O P O P O=

    O O

    C=2=2CC

    C=/

    PP

    C=2

    C=

    C=/

    C=2C=2

    C=/C

    C

    C=/

    C=

    far.e>i+%irofo*fat*i.teta>a

    C=2C

    C=/

    C=C=2O P O P O=

    O O

    O=O=

    far.e>i+%irofo*fat

    O= O=

    P O P O=

    O O

    C=C=2O

    C

    C=/

    C=2

    C

    C=/

    C==/CC=2

    C=2

    C

    C=/

    C=

    C=22

    CC=

    C=2C=2

    C

    C=/

    C=C=2

    C=2

    C

    C=/

    C=

    C=2C=2

    C=C

    C=2C=2

    C=C

    C=2C=2

    C=

    C=/

    CC=/

    =/C

    C=/

    C=/ C=/

    *cua+e.

    2( Tras%or!area sc&ale&l&i ? colesterol

    Sc!"#en!#

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    Biochimie farmaceutic

    O

    O2

    *cua+e. 2)/Le%o7i(u+*cua+e.u+ui

    =O

    +a.o*tero+u+

    *"no(tero#!# conine $ r!-ri 8eti# imo*tero+1L(ehi(ro(e*mo*tero+

    51

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    Biochimie farmaceutic

    C"ntit"te" de co#e(tero# e#i&er"t- de *D* deter8in- ,ite9"8et"&o#i(8!#!i co#e(tero#!#!i re#"re" #" ni,e# ce#!#"r "(tfe# e=ce(!#de co#e(tero# "c!8!#"t

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    Biochimie farmaceutic

    "tero"8e. Ace(t f"t d!ce #"

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    'ucia.a Do;o7ico+ic

    Din &i#- "ci9ii &i#i"ri (!nt de,er("i

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    Biochimie farmaceutic

    die(ti" i "&(or&i" #or rec!8 i " ,it"8ine#or#io(o#!&i#e: A D E i G.

    + Aci9ii &i#i"ri "cti,e"9- #i"9" "ncre"tic- i

    co#e(tero#e(ter"9" "ncre"tic-. De"(e8ene"

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    'ucia.a Do;

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    Biochimie farmaceutic

    4I(:( Aci+ii ,ra-i eseiali ;A5Eceto"cid!#!i "n"#o"8ino"cid!#!i inii"# i " "cid!#!i *+#!t"8ic.

    25

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    'ucia.a Do;a

    =/C C COO=

    =/C C= COO=

    =OOC C=2 C=2 C= COO=

    N=2

    O

    O

    C COO==OOC C=2 C=2

    N=2

    +euci.Ltra.*ami.a>a

    =/C C= C=2

    C=/

    COO=C

    O

    =/C C= C=2 C=

    C=/

    COO=

    N=2

    =OOC C=2 C=2 C= COO=

    N=2

    O

    C COO==OOC C=2 C=2

    tiro>i.Ltra.ami.a>a

    =O C=2 C COO=

    O

    =OOC C=2 C=2 C COO=

    O

    C= COO=

    N=2

    =OOC C=2 C=2

    N=2

    C=2 C= COO==O

    25

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    Biochimie farmaceutic

    Re"cii#e de tr"n("8in"re (!nt !or re,er(i&i#e e#e (e otde(f-!r"

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    Biochimie farmaceutic

    II.

    %iri(o7a+Lfo*fatLLe.>ima

    cetimi.a a+(imi.a

    %iri(o7ami.Lfo*fatLLe.>ima

    C= OE

    N=2

    COO=R2 C=

    =2O

    =2O

    E

    C=

    N

    COO=R2 C=

    E

    C=2

    N

    R2 C COO=

    =2O

    =2OE C=2 N=2

    O

    R2 C COO=

    ;irido="#+fo(f"t!# for8"t o"te (- reintre atra.*ami.a>a

    N=/=

    NAD=

    =2ONADcetoaci( -+utamat

    a+faLceto-+utaratami.oaci(

    22

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    Biochimie farmaceutic

    *+"8iono"cido=id"9" "re c" r!"re ro(tetic- N (trn(#e"t- de rotein" en9i8"tic-. Se -(ete

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    'ucia.a Do;a

    CO2

    C=2 N=2R

    COO=

    R C= N=2

    ;entr! c" re"ci" (- "i&- #oc i

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    Biochimie farmaceutic

    E=e8#e de re"cii de dec"r&o=i#"re:

    N

    N

    C=2 C= N=2

    =

    COO=

    CO2 =

    N

    N

    C=2 C= N=22

    hi*ti(i.a hi*tami.a

    =2C C=

    O=

    COO=

    N=2 CO2

    =2C C=2 N=2

    O=

    *eri.a co+ami.a

    hi(ro7i+a>a

    *eroto.i.a

    =N

    C=2 C=2 N=2=O

    CO2

    =O

    N

    C=2 C= COO=

    N=2

    =

    O2

    =N

    C=2 C= COO=

    N=2

    Din dec"r&o=i#"re" )i(tidinei tritof"n!#!i 3+)idro=itritof"n!#!i tiro9inei re9!#t- )i(t"8in" trit"8in"

    (erotonin" i tir"8in" c! ro# de )or8oni ti(!#"ri. Din dec"r&o=i#"re"treoninei ci(teinei i "cid!#!i "("rtic re9!#t- ro"no#"8in"ci(te"8in" P+"#"nin" c"re intr-

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    Biochimie farmaceutic

    A8oni"c!# rod!( #" ni,e#!# rinic)i#or deri,- din "8ino"ci9iiintr"ce#!#"ri i a

    N=2

    =OOC C=2 C=2 C= COO=

    N=/=2ON=2O

    =2N C C=2 C=2 C= COO=

    A8oni"c!# o"te fi e=cret"t (!& for8- de (-r!ri de "8oni!."re" 8"'orit"te e(te e=cret"t- (!& for8- de !ree c"re (e for8e"9-

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    'ucia.a Do;a

    -+utami. *i.teta>a

    aci( -+utamic=2O

    M-LADPaci( -+utamicM-LATP

    =2N C C=2

    O

    C=2 C= COO=

    N=2

    N="

    4II(6( Cicl&l &reo,eetic

    22

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    Biochimie farmaceutic

    ?n c!r(!# re"cii#or ce "#c-t!ie(c !n cic#! co8#et dintr+!n 8o#

    de "8oni"c re9!#t- !n 8o# de !ree i (e con(!8- $ 8o#i de AT;.Re"cii#e (!cce(i,e (!nt c"t"#i9"te de 3 en9i8e.C"r&"8oi# (intet"9" re9ent- a

    or.iti.a citru+i.a

    =/PO"O

    N=2C=2 N=

    C=2

    C=2

    C= N=2

    COO=

    C

    =O P O

    O

    C N=2

    O= O

    C=2 N=2

    C=2

    C=2C= N=2

    COO=

    ?n contin!"re citr!#in"

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    Biochimie farmaceutic

    ar-i.i.a or.iti.a uree

    O

    C N=2=2Nar-i.a>a

    =2O

    C=2 N=2

    C=2

    C=2

    C= N=2

    COO=

    C=2 N=

    C=2

    C=2

    C= N=2

    COO=

    C

    N=2

    N=

    Ornitin" re9!#t"t- o"te (- rei" !n no! cic#! i"r !ree" for8"t-e(te e=cret"t- !rin"r.

    Deci cic#!# !reoenetic e(te o c"#e 8et"&o#ic- fo"rteco(ti(ito"re entr! or"ni(8 deo"rece entr! fiec"re 8o#ec!#- de

    !ree ce (e for8e"9- (e con(!8- $ #e-t!ri 8"croerice.C"ntit"te" de !ree e=cret"t- de !n "d!#t nor8"# rin !rin- e(tede 23+$0

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    Biochimie farmaceutic

    Sc$e!a ,eeral' )e !etaboli+are a sc$elet&l&i )e ato!i )e C aia!ioaci+ilor

    I+e) Met)Thr)Va+

    +.) +u) =i*)Pro) Ar-

    Tr) Phe

    A*%) A*.

    I+e) 'eu) Tr

    Tr) 'eu) '*)Phe) Tr

    A+a) +) C*)Ser) Thr

    acetoaceti+8 CoAaci( %iruGic

    aci( ma+ic

    aci( o7a+i+acetic

    aci( fumaric

    aci( *ucci..ic

    *ucci.i+8 CoA

    aci( a+fa8 ceto-+utaric

    aci( i>ocitric

    aci( citric

    aceti+8 CoA

    De%ecte ? !etaboli+area a!ioaci+ilor

    ?n #e-t!r- c! 8et"&o#i(8!# "8inono"ci9i#or (!nt de(cri(e8"i 8!#te "feci!ni c"!9"te

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    Biochimie farmaceutic

    4II(8( Biosite+a a!ioaci+ilor

    Dintre "8ino"ci9ii c!no(c!i n!8"i !n n!8-r de 20 re9int-i8ort"n- entr! &io(inte9" roteine#or. Une#e for8e de ,i"t-#"nte &"cteriiB (!nt c""&i#e (- (inteti9e9e toi cei 20 de "8ino"ci9idin inter8edi"ri "8fi&o#ici. A#te#e inc#!(i, 8"8ifere#e i

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    'ucia.a Do;a

    5l&ta!ia (e (inteti9e"9- rintr+o re"cie c"t"#i9"t- de c-tre#!t"8in(intet"9- #ecnd de #" "cid *+#!t"8ic. Re"ci" nece(it-AT; c" i donor de enerie.

    COO=

    C= N=2

    FC=22

    COO=

    N="

    ATP ADP PM-2

    COO=

    C= N=2

    FC=22

    CON=2

    -+utami.*i.teta>a

    As*ara,ia(e (inteti9e"9- rintr+o re"cie (i8i#"r- #ecndde #" "cid *+ "("rtic (!& "ci!ne" ""r"in(intet"9ei AT; trece

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    Biochimie farmaceutic

    C=2 OPO/=2

    C= O=

    COO=

    =2O P

    C=2 O=

    C=

    COO=

    O=NAD NAD= =

    C=2 O=

    C O

    COO=

    AA A

    C=2 O=

    C

    COO=

    O

    NAD NAD= =

    C=2 OPO/=2

    C O

    COO= AA A

    C=2 OPO/=2

    C= N=2

    COO= =2O

    C"#e" rin inter8edi!# deri,"i#or fo(fori#"i nece(it-

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    Biochimie farmaceutic

    Ci(tein" (e (inteti9e"9- din *+(erin- i )o8oci(tein- c"rero,in c" inter8edi"ri a

    II

    I=O C=2 C= COO=

    N=2

    NADPNADP= =

    =2;io%teri.a=";io%teri.aN=2

    C=2 C= COO=

    Co8#e=!# feni#"#"nin )idro=i#"9ei re9int- do!- "cti,it"idi(tincte:5 > red!cere" o=ien!#!i 8o#ec!#"r #" "- i " feni#"#"ninei #" tiro9in-

    2 > red!cere" di)idro&ioterinei #" tetr")idro&ioterin- e (ocote"#"NAD;.*" fe# c" i ro#in" )idro=i#i9in" e(te re9ent-

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    'ucia.a Do;

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    Biochimie farmaceutic

    Hi)roli+a aci+ilor &cleici

    *"n!ri#e #!ni " "ci9i#or n!c#eici (!nt )idro#i9"te de c-tren!c#e"9e

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    'ucia.a Do;a(e>o7iri;o.uc+ea>a

    fo*fo(ie*tera>e

    .uc+eoti(a>afo*fomo.oe*tera>e

    .uc+eo>i(fo*fori+a>e

    Ca+ea%e.to>ofo*fatu+u

    R4LP(R4LP

    R!LP(R!LP

    P

    Ba>e %irimi(i.iceBa>e %uri.ice

    Nuc+eo>i(e

    P

    =2O4@LNuc+eoti(e

    =2O

    O+i-o.uc+eoti(e Nuc+eoti(e

    =2O

    'a.turi %o+i.uc+eoti(ice

    Catabolis!&l ,eeral al &cleoti)elor la ba+e *&riice -i*iri!i)iice

    N!c#eotide#e (!nt )idro#i9"te (ecific de c-tre 3H+n!c#eo9ide ifo(f"t. E=i(t- o 8"re ,"riet"te de "(e8ene" en9i8e !ne#e (ecret"tede 8!co"(" inte(tin"#- c! ro#

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    Biochimie farmaceutic

    n!c#eotid !rinic for8"t rin (inte9" de no,o i re9int- !n !nct de

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    'ucia.a Do;i(fo*fori+a>a

    =2N

    N

    N N

    N

    O=

    = =

    N

    N N

    N

    O

    =2N

    ==N

    N N

    N

    O

    =O=

    -ua.i>i.L4@Lfo*fat-ua.i>i.a

    -ua.i.a

    7a.ti.a

    -ua.a>a

    24

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    Biochimie farmaceutic

    N

    N N

    N

    O=

    O

    O=O=

    =2CO/PO82

    =2O P=2C

    O=

    O

    O=

    N

    N N

    N

    O=

    =O

    fo*fomo.oe*tera>a

    P RL!LP

    %uri.L.uc+eo>i(fo*fori+a>a

    N

    N N

    N

    O=

    = =

    N

    N N

    N

    O

    =

    i.o>i.L4@Lfo*fat i.o>i.a

    hi%o7a.ti.a

    =2OO2 =2O2

    NAD

    7a.ti.a

    =O =

    N

    N N

    N

    O

    =NAD=

    =

    ?n or"ni(8!# !8"n ="ntino=id"9" (e -(ete 8"i "#e(

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    'ucia.a Do;

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    *" o8 (e e#i8in- rin !rin-

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    for8e"9- 3H+fo(fori&o9i#+3+"8inoi8id"9o#. r!" N "d-!"t-

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    23

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    CO=2N

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    Se o"te o&(er," c- entr! (inte9" I; (e con(!8- "(e#e-t!ri 8"croerice con(idernd i for8"re" ;R;;.

    As*ecte )e *atolo,ie )i !etabolis!&l &cleoti)elor

    5&tae(te !n" din ce#e 8"i r-(ndite &o#i de 8et"&o#i(8 c!o frec,en- de 0$ din o!#"i" E!roei. S!& "ce(t- den!8ire (!ntinc#!(e !n r! )eteroen de &o#i c"r"cteri9"te to"te rin)ier!rice8ie c"re d!ce #" de!nere" !r"t!#!i de (odi!

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    4I/( Metabolis!&l $e!o,lobiei

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    "oi #" &i#i,erdin- c"re (!& "ci!ne" &i#i,erdin o=id"9ei i NAD; e(tetr"n(for8"t-

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