Ðåôåðàò: Íóêëå¿íîâ³ êèñëîòè
Ðåôåðàò: Íóêëå¿íîâ³ êèñëîòè
«Íóêëå¿íîâ³ êèñëîòè»
Ïëàí
1. Çàãàëüíà õàðàêòåðèñòèêà ³ ñêëàä íóêëåîïðîòå¿ä³â.
2. Ñòðóêòóðí³ åëåìåíòè íóêëå¿íîâèõ êèñëîò:
à). íóêëåîçèä;
á). íóêëåîòèä;
â). íóêëå¿íîâà êèñëîòà.
3. Êëàñèô³êàö³ÿ ³ áóäîâà íóêëå¿íîâèõ êèñëîò.
4. Á³îëîã³÷íà ðîëü íóêëå¿íîâèõ êèñëîò.
Íà îñîáëèâó óâàãó, çàâäÿêè âèêîíóâàíèì
ôóíêö³ÿì, çàñëóãîâóþòü ñêëàäí³ á³ëêè – íóêëåîïðîòå¿äè.
Íóêëåîïðîòå¿äè ì³ñòÿòüñÿ â êîæí³é êë³òèí
æèâîãî îðãàí³çìó, âõîäÿ÷è äî ñêëàäó êë³òèííèõ ÿäåð, ñóáêë³òèííèõ ñòðóêòóð.
Íóêëå¿íîâ³ êèñëîòè áóëè â³äêðèò
øâåéöàðñüêèì â÷åíèì ̳øåðîì ².Ô. ³ç ÿäåð êë³òèí ãíîþ ó âèãëÿä³ á³ëêîâî¿ ñïîëóêè
íóêëå¿íó.
Âèâ÷àþ÷è áóäîâó áóëî âñòàíîâëåíî, ùî ïðè
ã³äðîë³ç³ íóêëåîïðîòå¿äè ðîçïàäà-þòüñÿ íà á³ëêîâèé êîìïîíåíò òà íóêëå¿íîâ
êèñëîòè.
Íóêëåîïðîòå¿äè – ñêëàäí
á³ëêè ïðîñòåòè÷íîþ ãðóïîþ ÿêèõ º íóêëå¿íîâ³ êèñëîòè. Á³ëêîâèé òà ïðîñòåòè÷íèé
êîìïîíåíòè çâ‘ÿçàí³ ì³æ ñîáîþ çà äîïîìî-ãîþ åëåêòðîñòàòè÷íèõ, âîäíåâèõ
êîîðäèíàö³éíèõ çâ‘ÿçê³â.
 çàëåæíîñò³ â³ä áóäîâè ïðîñòåòè÷íî
ãðóïè, íóêëåîïðîòå¿äè ïîä³ëÿþòü íà :
äåçîêñèðèáîíóêëåîïðîòå¿äè – ïðîñòåòè÷íà ãðóïà ÿêèõ ÄÍÊ;
ðèáîíóêëåîïðîòå¿äè – ïðîñòåòè÷íîþ ãðóïîþ ÿêèõ º ÐÍÊ.
ßâëÿþ÷èñü ïðîñòåòè÷íèìè ãðóïàìè
íóêëåîïðîòå¿í³â ñàìå íóêëå¿íîâ³ êèñëîòè çáåð³ãàþòü (ÄÍÊ) ³ ïåðåäàþòü (ÐÍÊ)
ñïàäêîâó ³íôîðìàö³þ.
Íóêëå¿íîâ³ êèñëîòè – âèñîêîìîëåêóëÿðí³ îðãàí³÷í³ ñïîëóêè ÿê³ ïîáóäîâàí
ç âåëèêî¿ ê³ëüêîñò³ ìîíîíóêëåîòèä³â. Ïðè ã³äðîë³ç³ ðîçêëàäàþòüñÿ äî àçîòèñòèõ
îñíîâ, ïåíòîç ³ ôîñôîðíî¿ êèñëîòè.
 ã³äðîë³çàò³ íóêëå¿íîâèõ êèñëîò áóëî
çíàéäåíî 5 àçîòèñòèõ îñíîâ, äâ³ ç íèõ, àäåí³í ³ ãóàí³í – ïîõ³äí
ãåòåðîöèêë³÷íî¿ ñïîëóêè ïóðèíó òîìó ¿õ íàçèâàþòü ïóðèíîâèìè àçîòèñòèìè
îñíîâàìè:
                  NH2
OH
                 N N N
N N N
      N NH N NH H2N
N NH
ïóðèí àäåí³í
ãóàí³í
(6–àì³íîïóðèí) (2–àì³íî–6–îêñèïóðèí)
²íø
òðè – ïîõ³äí³ øåñòè÷ëåííîãî ãåòåðîöèêëó ï³ðèì³äèíó, òîìó ¿õ íàçèâàþòü ï³ðèì³äèíîâèìè îñíîâàìè (óðàöèë, òèì³í, öèòîçèí):
OH
OH NH2
                     
CH3
          N N N
N
      
N HO N HO N
HO N
ï³ðèì³äèí óðàöèë òèì³í öèòîçèí
Óðàöèë çà ñèñòåìàòè÷íîþ íîìåíêëàòóðîþ ìຠíàçâó – (2,4-äèîêñ³ï³ðèì³äèí), òèì³í
(5-ìåòèë-2,4-äèîêñ³ï³ðèì³äèí), öèòîçèí – (2– îêñ³–4–àì³íîï³ðèì³äèí).
Êð³ì àçîòèñòèõ îñíîâ â ã³äðîë³çàò³ òàêîæ
çíàéøëè çàëèøêè ïåíòîç, à ñàìå ðèáîçè ³ äåçîêñèðèáîçè ó âèãëÿä³ –àíîìåð³â:
    HOCH2 O OH
HOCH2 O OH
      H H
H H
     H H H
H
OH OH HO H
–ðèáîôóðàíîçà –äåçîêñèðèáîôóðàíîçà
Ïîð³âíþþ÷è ÿê³ñíèé ³ ê³ëüê³ñíèé ñêëàä ã³äðîë³çàò³â íóêëå¿íîâèõ êèñëîò, â÷åí³ ïîì³òèëè äåÿê³ â³äì³ííîñò³:
I–é òèï ã³äðîë³çàò³â II–é òèï ã³äðîë³çàò³â
Äåçîêñèðèáîçà Ðèáîçà
àäåí³í àäåí³í
ãóàí³í ãóàí³í
öèòîçèí öèòîçèí
ôîñôîðíà êèñëîòà ôîñôîðíà
êèñîòà
òèì³í óðàöèë
I–é òèï ã³äðîë³çàò³â ì³ñòèòü âóãëåâîä
äåçîêñèðèáîçó, òîìó ö³ëèé ðÿä íóêëå¿íîâèõ êèñëîò ùî ìàþòü ã³äðîë³çàò òàêîãî
òèïó áóëî íàçâàíî äåçîêñèðèáîíóêëå¿íîâè-ìè (ÄÍÊ).
II–é òèï ã³äðîë³çàò³â ì³ñòèòü
âóãëåâîäíåâèé êîìïîíåíò ðèáîçó, òîìó íóêëå¿íîâ³ êèñëîòè ùî éîãî ì³ñòÿòü
íàçèâàþòü ðèáîíóêëå¿íîâèìè (ÐÍÊ) êèñëîòàìè.
Ñòðóêòóðíîþ ÷àñòèíîþ íóêëå¿íîâî¿ êèñëîòè º íóêëåîòèä äî ñêëàäó ÿêîãî
âõîäÿòü àçîòèñòà îñíîâà, âóãëåâîä ³ ôîñôîðíà êèñëîòà.
 ðåçóëüòàò³ âçàºìî䳿 ã³äðîêñèëó
âóãëåâîäó (ðèáîçè ÷è äåçîêñèðèáîçè) ÿêèé çíàõîäèòüñÿ á³ëÿ ïåðøîãî àòîìà âóãëåöþ
ç àòîìîì âîäíþ á³ëÿ 9-ãî àòîìà àçîòó àçîòèñòî¿ îñíîâè ç óòâîðåííÿì íîâîãî
çâ‘ÿçêó N–H ( â ðåçóëüòàò³ â³äùåïëåííÿ ìîëåêóëè âîäè), óòâîðþºòüñÿ íóêëåîçèä.
      NH2
    
N N
 
N N
 H
  HOCH2 O OH
  H H
  H H
OH OH
      NH2
    
N N
  
N N
+
H2O
  HOCH2 O
  H H Íóêëåîçèä – àäåíîçèí
  H H
OH OH
ßêùî
â óòâîðåíí³ íóêëåíîçèäó áåðå ó÷àñòü àçîòèñòà îñíîâà ãóàí³í,
òî íóêëåîçèä áóäå ìàòè íàçâó
ãóàíîçèí; ÿêùî óðàöèë – óðèäèí; öèòîçèí – öèòèäèí; òèì³í – òèì³äèí.
 ðåçóëüòàò³ ïðèºäíàííÿ ôîñôîðíî¿ êèñëîòè äî 5–¿ ã³äðîêñèëüíî¿ ãðóïè ïåíòîçè â ñêëàä³ íóêëåîçèäó çà ðàõóíîê ñêëàäíîåô³ðíîãî çâ‘ÿçêó, óòâîðþºòüñÿ ñòðóêòóð-íà ÷àñòèíà íóêëå¿íîâî¿ êèñëîòè – íóêëåîòèä.
         NH2
  N
N
     OH
N N
HO–P=O
+ OH
  HOCH2 O
  H H
  H H
OH OH
      NH2
    
N N
    OH
N N
 O=P
OH O +
H2O
  CH2 O
  H H Íóêëåîòèä – àäåí³ëîâà
êèñëîòà.
  H H
OH OH
ßêáè â óòâîðåíí³ íóêëåîòèäó áðàâ ó÷àñòü
íóêëåîçèä ãóàíîçèí, òî íàçâà íóêëåî-òèäó áóëà á â³äïîâ³äíî – ãóàí³ëîâà êèñëîòà;
óðèäèí – óðèäèëîâà êèñëîòà; öèòèäèí – öèòèäèíîâà êèñëîòà; òèì³äèí – òèì³äèíîâà
êèñëîòà.
Äî ñêëàäó ìîëåêóëè íóêëå¿íîâî¿ êèñëîòè
ìîæå âõîäèòè â³ä 80 äî 1000000 íóêëåîòèäíèõ çàëèøê³â ÿê³ çâ‘ÿçóþòüñÿ ì³æ ñîáîþ
çâ‘ÿçêàìè, ùî óòâîðþþòüñÿ â ðåçóëüòàò³ âçàºìî䳿 3-¿ ñïèðòîâî
ãðóïè ïåíòîçè îäíîãî íóêëåîòèäó òà ôîñôîð-íîãî ã³äðîêñèëó ùî çíàõîäèòüñÿ á³ëÿ
5-ãî àòîìà âóãëåöþ ïåíòîçè äðóãîãî íóêëåîòèäó, óòâîðþþ÷è ïðè öüîìó ìîëåêóëó
íóêëå¿íîâî¿ êèñëîòè. Îñòàííÿ ÿâëÿºòüñÿ ïðîñòåòè÷íîþ ãðóïîþ íóêëåîïðîòå¿äó,
á³ëêîâîþ ÷àñòèíîþ ÿêîãî íàé÷àñò³øå âèñòóïàþòü ïðîòàì³íè ³ ã³ñòîíè.
      NH2
    
N N
    OH
N N
 O=P
OH O Íóêëåîòèä – àäåí³ëîâà êèñëîòà
  CH2 O
  H H
  H H
 OH OH
      OH
     + N
N
    OH H2N
N N
 O=P
OH O
  CH2 O
  H H Íóêëåîòèä – ãóàí³ëîâà êèñëîòà.
  H H
OH OH
         NH2
  N
N
    OH
N N
 O=P
OH O
  CH2 O
  H H
  H H
OH
      OH
      Î N
N
    H2N
N N + Í2Î
O=P
OH O
  CH2 O
  H H Äèíóêëåîòèä
  H H
OH OH
Îòæå: íóêëå¿íîâ³ êèñëîòè – ïðèðîäí
á³îïîë³ìåðè ÿê³ ñêëàäàþòüñÿ ç äóæå âåëèêî¿ ê³ëüêîñò³ íóêëåîòèä³â (ìîíîìåð³â).
ÄÍÊ ³íñóë³íó ëþäèíè ñêëàäàºòüñÿ ç 2860
íóêëåîòèä³â;
ÄÍÊ ñîìàòîòðîï³íó – 15000 íóêëåîòèä³â;
ÄÍÊ ì³òîõîíäð³é – 30000 íóêëåîòèä³â.
Ïîñê³ëüêè íóêëå¿íîâ³ êèñëîòè º ñêëàäíèìè
á³ëêàìè, òî äëÿ íèõ òàêîæ âëàñòèâèé âèñîêèé ð³âåíü îðãàí³çàö³¿.
ϳä ïåðâèííîþ ñòðóêòóðîþ
ðîçóì³þòü ïîðÿäîê ÷åðãóâàííÿ íóêëåîòèä³â ó ïîë³-íóêëåîòèäíèõ ëàíöþãàõ.
Äëÿ êîæíî¿ íóêëå¿íîâî¿ êèñëîòè õàðàêòåðíà
ñâîÿ ïåðâèííà ñòðóêòóðà, ÿêà ³ âèçíà÷ຠâèäîâó ñïåöèô³÷í³ñòü æèâèõ îðãàí³çì³â.
Áóäîâà ÄÍÊ
Ïîñê³ëüêè ÄÍÊ – ñêëàäí³ á³ëêè
íóêëåîïðîòå¿äè, òî âîíè õàðàêòåðèçóþòüñÿ âåëè-êèìè
ìîëåêóëÿðíèìè ìàñàìè (100000–3000000) òà âåëèêîþ ê³ëüê³ñòþ ìîíî-íóêëåîòèä³â
(80 – 100000).
Âñ³ ìîíîíóêëåîòèäè ÿê³ñíî ïðåäñòàâëåí
4-ìà ïðåäñòàâíèêàìè äî ñêëàäó ÿêèõ âõîäèòü äåçîêñèðèáîçà: äåçîêñèàäåí³ëîâà
êèñëîòà (À), äåçîêñèãóàí³ëîâà êèñëîòà (Ã), äåçîêñèöèòèäèíîâà (Ö),
äåçîêñèòèì³äèíîâà (Ò).
Çâ‘ÿçóþ÷èñü ì³æ ñîáîþ 3–5 ôîñôîåô³ðíèìè
çâ‘ÿçêàìè âîíè óòâîðþþòü ïîë³-íóêëåîòèäíèé ëàíöþã ÄÍÊ.
Äîñë³äæóþ÷è áóäîâó ìîëåêóëè ÄÍÊ çà
äîïîìîãîþ ðåíòãåíîñòðóêòóðíîãî, òà ³í-øèõ âèä³â àíàë³çó, áóëî
âñòàíîâëåíî ùî:
1. Ìîëåêóëà ÄÍÊ ñêëàäàºòüñÿ ç äâîõ àíòèïàðàëåëüíèõ ëàíöþã³â.
2. Àçîòèñò³ îñíîâè îáîõ ïîë³ïåïòèäíèõ ëàíöþã³â
çíàõîäÿòüñÿ â ñåðåäèí³ óÿâíîãî ïðîñòîðîâîãî öèë³íäðó, ïåíòîçè òà çàëèøêè
ôîñôîðíî¿ êèñëîòè – ççîâí³.
3. Àçîòèñò³ îñíîâè ïîë³ïåïòèäíèõ ëàíöþã³â ðîçì³ùåí³ ïî
ïðèíöèïó êîìïëåìåí-òàðíîñò³ (âçàºìîäîïîâíåííÿ). Öÿ çàêîíîì³ðí³ñòü â³äîìà
ï³ä íàçâîþ ïðàâèëà ×àðãàôôà.
Ïðàâèëî ×àðãàôôà
3.1.Ïóðèíîâ³ àçîòèñò³ îñíîâè îäíîãî ïîë³ïåïòèäíîãî ëàíöþãà ðîçì³ùóþòüñÿ ïðîòè ï³ðèì³äèíîâèõ îñíîâ äðóãîãî ïîë³ïåïòèäíîãî ëàíöþãà. Àäåí³í ïðîòè òèì³íó (ñòàá³ë³çóºòüñÿ äâîìà âîäíåâèìè çâ‘ÿçêàìè); ãóàí³í ïðîòè öèòîçèíó (ñòàá³ë³çóºòüñÿ òðüîìà âîäíåâèìè çâ‘ÿçêàìè).
Íàñë³äêè ïðàâèëà ×àðãàôôà
 ìîëåêóë³ ÄÍÊ ñóìà ïóðèíîâèõ îñíîâ ð³âíà
ñóì³ ï³ðèì³äèíîâèõ: À+Ã=Ò+Ö;
=1
ʳëüê³ñòü àäåí³íó äîð³âíþº ê³ëüêîñò
òèì³íó (À=Ò), ãóàí³íó äîð³âíþº öèòîçèíó (Ã=Ö). Ñï³ââ³äíîøåííÿ ñóì ïàð À+Ò ³ Ã+Ö
íîñèòü íàçâó êîåô³ö³ºíòà ñïåöè-ô³÷íîñò³ ³ º îäí³ºþ ç íàéâàæëèâ³øèõ
õàðàêòåðèñòèê ÄÍÊ. Êîåô³ö³ºíò ñïåöèô³÷-íîñò³ áóâ â³äêðèòèé ó 1962 ðîö
Á³ëîçåðñüêèì ³ Ñï³ðê³íèì ³ ñóòü éîãî ïîëÿãຠó ñë³äóþ÷îìó:
 1) ßêùî  1, òî ìîëåêóëà ÄÍÊ
ÀÒ–òèïó, õàðàêòåðíà äëÿ îðãàí³çì³â âèùèõ òâàðèí òà ðîñëèí.
 2) ßêùî 1, òî
ìîëåêóëà ÄÍÊ ––ÃÖ–òèïó, õàðàêòåðíà äëÿ ì³êðîîðãàí³çì³â.
Îòæå:1.Ìîëåêóëà ÄÍÊ âîëî䳺 ïåðâèííîþ,
âòîðèííîþ, òðåòèííîþ ñòðóêòóðàìè.
2.ÄÍÊ– ëîêàë³çîâàíà â õðîìîñîìàõ êë³òèííèõ
ÿäåð.
3.ÄÍÊ çâ‘ÿçàí³ ç á³ëêàìè îñíîâíîãî
õàðàêòåðó – ã³ñòîíàìè.
4.ÄÍÊ çäàòí³ äî ñàìîâ³äòâîðåííÿ â
ðåçóëüòàò³ ïðîöåñó ðåïë³êàö³¿.
5.ÄÍÊ–îñíîâíèé íîñ³é ³íôîðìàö³¿ ïðî áóäîâó
ñòðóêòóðó á³ëê³â îðãàí³çìó.
Áóäîâà ÐÍÊ
Ìr(ÐÍÊ)=10000–16000000. Ïîë³íóêëåîòèä ÐÍÊ
ì³ñòèòü 2–3000000 ìîíîíóêëåî-òèä³â. Â÷åí³ âñòàíîâèëè ùî:
1. Äî ñêëàäó íóêëåîòèä³â ÐÍÊ âõîäèòü
ðèáîçà.
2. Íóêëåîòèäè ÿê³ñíî ïðåäñòàâëåí
àäåí³ëîâàîþ, ãóàí³ëîâîþ, öèòèäèíîâîþ òà óðàöèëîâîþ êèñëîòàìè.
3. Íóêëåîòèäè çâ‘ÿçàí³ ì³æ ñîáîþ 3–5 ôîñôîåô³ðíèìè
çâ‘ÿçêàìè â îäíîëàíöþãî-âèé ïîë³ïåïòèäíèé ëàíöþã.
4. Ïîë³ïåïòèäíèé ëàíöþã ñï³ðàë³çîâàíèé ëèøå íà êîðîòêèõ
ä³ëÿíêàõ.
5. Îñíîâíå ì³ñöå ëîêàë³çàö³¿ – âíóòð³êë³òèííèé ïðîñò³ð.
6. ʳëüê³ñòü ÐÍÊ ïîñò³éíî çì³íþºòüñÿ ³ çàëåæèòü â³ä
íòåíñèâíîñò³ ïðîöåñ³â ñèíòåçó á³ëêà.
Çàëåæíî â³ä âèêîíóâàíèõ ôóíêö³é ìîëåêóëè
ÐÍÊ ïîä³ëÿþòüñÿ íà :
Ìàòðè÷í³ ÐÍÊ (Ìr =25000–1000000) – ì³ñòÿòü â³ä 75 äî 3000
íóêëåîòèä³â. Ñòàíîâëÿòü 2 % â³ä çàãàëüíîãî âì³ñòó ÐÍÊ êë³òèíè. Âèñòóïàþòü
ïîñåðåäíèêàìè ì³æ ìîëåêóëàìè ÄÍÊ òà ÐÍÊ ðèáîñîì íà ÿêèõ â³äáóâàºòüñÿ á³îñèíòåç
á³ëêà. Øâèäêî ñèíòåçóþòüñÿ ³ ðîçïàäàþòüñÿ.
Òðàíñïîðòí³ ÐÍÊ (Ìr=25000–31000) – ì³ñòÿòü 70–90 íóêëåîòèä³â.
Ñòàíîâëÿòü 10 – 15 % âñ³õ ÐÍÊ êë³òèíè. Òðàíñïîðòóþòü àì³íîêèñëîòè äî ì³ñöÿ
çáîðêè ìîëåêóëè á³ëêà.
Ðèáîñîìàëüí³ ÐÍÊ (Ìr= 500000–16000000) ì³ñòÿòü 1500–4500 íóêëåîòèä³â.
Ñòàíîâëÿòü 80–90% âñ³õ ÐÍÊ êë³òèíè. ̳ñòÿòüñÿ â ðèáîñîìàõ (îðãàíî¿ä äå
ïðî-õîäèòü á³îñèíòåç á³ëêà). ¯õ ðîëü äî ê³íöÿ íå ç‘ÿñîâàíà.
Îòæå: ìîëåêóëè ÄÍÊ º íîñ³ÿìè ³íôîðìàö
ïðî áóäîâó ³ ñòðóêòóðó á³ëê³â; ìîëåêóëè ÐÍÊ ñïðèÿþòü òî÷íîìó çíÿòòþ ³íôîðìàö
ç ÄÍÊ ³ â³äòâîðåíí³ ¿¿ â ìîëåêóë³ á³ëêà.
Ïèòàííÿ äëÿ ñàìîêîíòðîëþ.
1.Ñêëàä íóêëåîïðîòå¿ä³â ÄÍÊ.
2.Ñêëàä íóêëåîïðîòå¿ä³â ÐÍÊ.
3.Ïîíÿòòÿ íóêëåîçèäó ³ íóêëåîòèäó.
4.Êëàñèô³êàö³ÿ íóêëå¿íîâèõ êèñëîò.
5.Áóäîâà òà ð³âí³ îðãàí³çàö³¿ ÄÍÊ.
6.Áóäîâà òà ð³âí³ îðãàí³çàö³¿ ÐÍÊ.
7. Ïðàâèëà ×àðãàôôà, éîãî íàñë³äêè.
8. Ñóòü êîåô³ö³ºíòó ñïåöèô³÷íîñò³.
9. Âèäè ÐÍÊ òà ôóíêö³¿ ÿê³ âîíè âèêîíóþòü.
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