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Nucleotide metabolism (De novo synthesis of purine (嘌呤環上N的來源 (image, N…

- - - - 酵素
        
        PRPP synthetase / ribose-5-phosphate pyrophosphokinase
      - 反應
        
        ribose-5-phosphate → PRPP
      - Rate-limiting step
    - - 加 glutamine
      - 反應
        
        PRPP → phosphoribosyl-β-amine
      - 酵素
        
        Gln:PRPP amino-transferase
      - First-committed step
    - - 反應
        
        FAICAR →inosine monophosphate (IMP)
      - 酵素
        
        IMP synthase
  - - - STEP 3.4.6
    - - STEP 7.8
    - - STEP 10.11
  - - - STEP 1
        
        反應
        
        IMP + aspartate → adenylsuccinate
        
        酵素
        
        adenylsuccinate synthetase
        
        需要GTP
      - STEP 2
        
        反應
        
        adenylsuccinate → AMP + fumerate
        
        酵素
        
        adenylsuccinase / adenylsuccinate lyase
    - - STEP 1
        
        反應
        
        IMP → XMP
        
        酵素
        
        IMP dehydrogenase
      - STEP 2
        
        反應
        
        XMP → GMP
        
        酵素
        
        GMP synthetase
        
        需要ATP
  - - - R-5-P pyrophosphokinase
        
        ADP & GDP (-)
      - Gln:PRPP aminotransferase
        
        AMP, ADP, ATP & GMP, GDP,GTP & IMP (-)
        
        PRPP (+)
    - - adenylsuccinate synthetase
        
        AMP (-)
    - - IMP dehydrogenase
        
        GMP (-)
  - - - AMP + ATP → 2ADP
        
        酵素：adenylate kinase
      - GMP + ATP → GDP + ADP
        
        酵素： guanylate kinase
    - - all NDP + ATP → NTP + ADP
- - - - glutamine + HCO3- + 2ATP + H2O → carbamoyl phosphate + glutamate
      - 酵素
        
        carbamoyl phosphate synthase II (CPS II)
    - - carbamoyl-P + aspartate → carbamoyl-Asp
      - 酵素
        
        aspartate transcarbamoylase (ATCase)
    - - carbamoyl-Asp → dihydroorotate (DHO) + OH-
      - 酵素
        
        dihydroorotase
    - - DHO → orotate (一種嘧啶)
      - 酵素
        
        DHO dehydrogenase
    - - orotate + PRPP → orotidine 5'-monophosphate (OMP)
      - 酵素
        
        orotate phosphoribosyltransferase
    - - OMP → UMP + CO2
      - 酵素
        
        OMP decarboxylase
  - - - UMP + ATP → UDP + ADP
      - 酵素
        
        nucleoside monophosphate kinase
    - - UDP + ATP → UTP + ADP
      - 酵素
        
        nucleoside diphosphate kinase
    - - UTP + glutamine + ATP → CTP + glutamate
      - 酵素
        
        CTP synthetase
  - - - CPS II
        
        PRPP, IMP, ATP (+)
        
        UDP, UTP (-)
    - - ATCase
        
        ATP (+)
        
        CTP (-)
- - - - 3 nucleotide binding sites
        
        C：substrate (active site)
        on R2
        
        NDPs
        
        A：activity-determining (overall activity site)
        on R1
        
        ATP(+) & dATP(-)
        
        S：specificity-determining (substrate specific site)
        on R1
        
        ATP
        
        偏向反應
        
        CDP, UDP
        
        dTTP
        
        偏向反應
        
        GDP, ADP
        
        dGTP
        
        偏向反應
        
        ADP
        
        dATP
      - α2β2
      - Tyr122 free radical
        1>> removal of Ha hydrogen(Cys439)
        2>> creation of C-3' redical
      - disulfide formation between Cys225 & Cys462
        1>> dehydration
        2>> form dNTP
  - - - nucleoside kinase 將其轉為dAMP → dATP
        
        dATP 抑制 ribonucleotide reductase
        
        無法合成dNTP, 無法複製DNA
- - - - β-alanine, ammonium, CO2
  - - - β-aminoisobutyric acid (BAIBA), ammonium, CO2
- - - - allopurinol 可抑制 xanthine oxidase
- - - - N10-formyl-THF
- - - - purine nucleoside
        phosphorylase (PNP)
        
        hypoxanthine
        
        xanthine oxidase
- - - - xanthine
        
        xanthine oxidase
        
        uric acid
- - - - guanine
        
        guanine deaminase
- - - - → dUMP → dTMP
  - - - → dUMP → dTMP