Biosynthesis of Purine

of Purine


       At the end of this lecture, student will be able to

       Explain biosynthesis of purine

       Explain salvage pathway

       Describe degradation of purine

consequences of defective purine metabolism

Biosynthesis of purine nucleotides

major routes for purine nucleotide biosynthesis

       Many compounds contribute to purine
ring of nucleotides

       N1 of purine is derived
from Aspartate

       C2 & C8
arise from N10-Formyl THF

       N3 &N9 from

       C4, C5 & C7
from glycine

       C6 directly comes from CO2

       Major site of purine synthesis is in
the liver

       Purines are actually synthesised as

       Synthesis of the purine nucleotides
begins with PRPP and leads to the first fully formed nucleotide, IMP

       The purine base without the attached
ribose moiety is hypoxanthine

        The purine base is built upon the ribose by
several amidotransferase and transformylation reactions

       Synthesis of IMP requires five moles
of ATP, two moles of glutamine, one mole of glycine, one mole of CO2,
one mole of aspartate and two moles of formate

  1. Liver is the major organ for
    purine nucleotide synthesis

  2. Ribose 5P obtained by
    carbohydrate metabolism is the precursor for synthesis of purine
    nucleotides. It react with ATP to form Phosphoribosyl pyrophosphate (PRPP)
    in presence of PRPP synthetase

  3. Glutamine transfers its amide
    to PRPP to replace pyrophosphate & produce
    β-5-phosphoribosyl amine

  4. Phosphoribosyl amine react with
    glycine in presence of ATP to form glycin amide ribosy-5-phosphate  

  5. N10 formyl THF
    donate the formyl group & produce formyl glycin amide ribosyl -5-

  6. Glutamine transfer the second
    amide group to form formyl glycin amide ribosyl -5- phosphate

  7. The imidazole ring is closed in
    an ATP dependent reaction to yield 5-amino-imidazole ribosyl -5- phosphate

  8. Incorporation of Co2
    occurs to yield amino imidazole carboxylate ribosyl -5- phosphate

  9. Aspartate  condenses to form amino imidazole-4-
    succinyl carboxamide ribosyl -5- phosphate

  10. Adenosuccinatelyase cleaves of
    fumarate and only the amino group of aspartate is retained to yield amino
    imidazole -4- carboxamide ribosyl -5- phosphate
  1. N10-Formyl THF
    donate a one carbon moiety to produce 5 formyl amino imidazole -4-
    carboxamide ribosyl-5- posphate . With this reaction all the carbon &
    nitrogen atoms of purines ring are obtained

  2. Formyl amino imidazole -4-
    carboxamide ribosyl-5- phosphate catalysed by cyclohydrolase and leads to
    close ring with elimination of H2O molecule to form Inosine

  3. IMP is the immediate precursor
    for formation of GMP & AMP

  4. Aspartate condenses with IMP in
    presence of GTP to produce Adenyl   
    succinate which cleavage to form AMP

  5. IMP undergoes NAD dependent
    dehydrogenation to form AMP and glutamine then combines with XMP and forms

       IMP (parent nucleotide) does not
accumulate in cells but is rapidly converted to other purine nucleoside
monophosphates AMP (adenosine monophosphate) & GMP (guanosine

       IMP represents a branch point for
purine biosynthesis, because it can be converted into either AMP or GMP through
two distinct reaction pathways

       The pathway leading to AMP requires
energy in the form of GTP; that leading to GMP requires energy in the form of

Salvage pathway

Phosphoribosyl transferases involved in salvage
pathway convert free bases to nucleotides

can be directly converted to the corresponding nucleotides

       Regulation of purine biosynthesis is
based on the availability of intracellular concentration of PRPP, PRPP synthase
and ribose -5- Phosphate

Catabolism of Purine nucleotides

Disorders of defective purine metabolism

1. Hyperuricemia:

uric acid is the end product of purine

Normal concentration in serum is 2.5 -7mg / dl
in men & 1.5-6mg/dl in women

Elevation in serum level referred as

2. Gout:

diseases associated with over production of uric acid, where crystals of sodium
urate gets deposited in soft tissue like joints. Such deposit is known as tophi
and leads to gouty arthritis

common in men than in women

types of gout:

gout: In born error of metabolism due to over production of uric acid
(treatment by Allopurinol etc)

of primary gout is due to excessive production of purines and to renal
retention of uric acid

purine synthesis is due to deficiency of hypoxanthine-guanine phosphoribosyl

: Due to various diseases which causes increased synthesis or decreased
excretion of uric acid

       Increased degradation of nucleic
acids (hence more uric acid formation) is observed in various cancers
(leukemias, polycythemia, lymphomas, etc.) psoriasis and increased tissue
breakdown (trauma, starvation etc.)

       Disorders associated with impairment
in renal function cause accumulation of uric acid which may lead to gout


major sources of nucleotides are salvage pathway and de novo biosynthesis

nucleotides are biodegraded by nucleotidases, nucleotide phosphorylases,
deaminases & xanthine oxidase

acid is the final product of purine biodegradation in mammals

purine metabolism leads to clinical disease

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