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    Purine Metabolism II: Osama Yousef

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    Wan Nurfazliyana
    This document summarizes purine metabolism, including: 1. The purine salvage pathway which recycles purine bases through the actions of APRT and HGPRT enzymes. 2. The synthesis of deoxyribonucleotides from ribonucleotides by ribonucleotide reductase during DNA replication. 3. The degradation of purine nucleotides through various enzymes, ultimately producing uric acid, and the intestinal degradation of dietary nucleic acids into absorbable nucleosides and bases.

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    Purine Metabolism II: Osama Yousef

    Uploaded by

    Wan Nurfazliyana
    72 views14 pages
    This document summarizes purine metabolism, including: 1. The purine salvage pathway which recycles purine bases through the actions of APRT and HGPRT enzymes. 2. The synthesis of deoxyribonucleotides from ribonucleotides by ribonucleotide reductase during DNA replication. 3. The degradation of purine nucleotides through various enzymes, ultimately producing uric acid, and the intestinal degradation of dietary nucleic acids into absorbable nucleosides and bases.

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    Purine Metabolism II

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    This document summarizes purine metabolism, including: 1. The purine salvage pathway which recycles purine bases through the actions of APRT and HGPRT enzymes. 2. The synthesis of deoxyribonucleotides from ribonucleotides by ribonucleotide reductase during DNA replication. 3. The degradation of purine nucleotides through various enzymes, ultimately producing uric acid, and the intestinal degradation of dietary nucleic acids into absorbable nucleosides and bases.

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    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    72 views14 pages

    Purine Metabolism II: Osama Yousef

    Uploaded by

    Wan Nurfazliyana
    This document summarizes purine metabolism, including: 1. The purine salvage pathway which recycles purine bases through the actions of APRT and HGPRT enzymes. 2. The synthesis of deoxyribonucleotides from ribonucleotides by ribonucleotide reductase during DNA replication. 3. The degradation of purine nucleotides through various enzymes, ultimately producing uric acid, and the intestinal degradation of dietary nucleic acids into absorbable nucleosides and bases.

    Copyright:

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    Download as PPTX, PDF, TXT or read online from Scribd
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    of 14

    Purine Metabolism II

    Osama Yousef
    Purine Metabolism II
    • Purine salvage pathway
    • Synthesis of Deoxyribonucleotides
    • Nucleotides degradations
     Intestinal degradation of dietary nucleic acids
     Degradation of purine nucleotides
    Purine salvage pathway
    Salvage pathway: synthesize of purine neocletide from the
    partial breakdown of previously synthesized nucleotides
    (turnover of cellular nucleic acids, or diet)

    • Two phosphoribosyl transferases are involved:


    – APRT (adenine phosphoribosyl transferase) for adenine
    – HGPRT (hypoxanthine guanine phosphoribosyl
    transferase) for guanine or hypoxanthine
    – Both APRT and HGPRT use PRPP to form the
    nucleotides.
    Adenine phosphoribosyl transferase (APRT)

    OH

    OH P O CH2 H
    O
    O O
    O H H adenine
    H O P O P O-
    OH OH PPi
    O- O-

    PRPP NH2

    N
    N

    OH N N
    OH P O CH2
    O
    O H H
    H H
    OH OH
    Hypoxanthine guanine phosphoribosyl transferase
    (HGPRT)
    Lesch-Nyhan syndrome
    • X-linked recessive disorder
    • Associated with complete deficiency of HGPRT
    enzyme in ability to salvage hypoxanthine or
    guanine
    • Increase PRPP level, and decrease IMP and GMP
    levels
    • Increase rate of de novo pathway for purine
    synthesis is about 200X
    • Increase uric acid level (Hyperuricemia)  Gout
    • patients show mental aberrations, motor
    dysfunction, behavioral disturbance (self-mutilation
    by biting lips and fingers)
    Synthesis of Deoxyribonucleotides
    • Amount of RNA (mRNAs, rRNAs and
    tRNAs) in the typical cell is 5-10 times of
    DNA amount.
    • During the S-phase of cell cycle,
    ribonucleoside diphosphates (ADP, GDP,
    CDP, UDP)  deoxyribonucleoside
    diphosphates (dADP, dGDP, dCDP, dUDP)
    by ribonucleotide reductase.
    • dNDP  dNTP (by nucleoside diphosphate
    kinases )
    Synthesis of Deoxyribonucleotides
    Regeneration of Ribonucleotide Reductase
    Regulation of Ribonucleotide Reductase
    • The enzyme is a tetramer (dimer of dimers): R1 – a dimer of
    identical a subunits, and R2 – a dimer of identical b subunits
    (45 kD each)
    3 binding sites
    1- Active site for binding of RNDP (ADP, GDP, CDP, UDP)
    2- Activity sites for binding of ATP and dATP
    ATPactivate the enzyme
    dATP inhibits the enzyme
    3- Substrate specificity site for binding of ATP, dATP, dTTP,
    dGTP 
    Binding of one regulate reduction of specific ribonucleotide.
    (eg. Binding of dTTP stimulate reduction of GDP to dGDP)
    Regulation of Ribonucleotide Reductase
    Nucleotides degradations
    Intestinal degradation of dietary nucleic acids
    1) Cleavage begins at the phosphodiester bonds with
    endonucleases (pancreatic ribonuclease or DNase) in the small
    intestine.
    2) The oligonucleotides resulting from previous action are then
    cleaved by phosphodiesterases, producing 5' or 3'
    monophosphates.
    3) Nucleotidases cleave phosphates from the nucleotides,
    yielding nucleosides. (could be absorbed)
    4) Nucleoside phosphorylases act to yield a base and ribose-1-
    phosphate.
    5) If bases or nucleosides are not reused for nucleic acid
    synthesis via salvage pathways, the bases are further degraded
    to uric acid (purines) or –alanine and NH3 (pyrimidines).
    Degradation of purine nucleotides
    1) Deaminases: AMP IMP
    Adenosine  Inosine
    2) 5’-nucleotidases: GMP  Guanosine
    IMP  Inosine
    3) Purine nucleoside phosphorelase:
    InosineHypoxanthin
    Guanosine Guanine
    4) Guanase: Guanine Xanthine (deamination)
    5) Xanthine oxidase: Hypoxanthine  Xanthine
    Xanthine  Uric Acid
    Degradation of purine nucleotides

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