Biosynthesis of purine 1st sem MSc

1. Biosynthesis of purine

2. Purine
 Purine is a heterocyclic aromatic organic compound that consists of two
rings. It is water-soluble. Purine also gives its name to the wider class of
molecules, purines, which include substituted purines and their tautomers.
They are the most widely occurring nitrogen-containing heterocycles in
nature.
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3. Pathways for purine nucleotide synthesis
1)De-novo synthesis
Biochemical pathway where nucleotides are
synthesized from new simple precursor molecule.
2) Salvage pathway
Used to recover bases and nucleotides formed
during the degradation of RNA and DNA.
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5. De-novo synthesis of purine
 N1 from amino acid Aspartate
 C2 and C8 from formate of N10-formyl THF
 N3 and N9 from amine group glutamine
 C4,C5,N7 from Glycine
 C6 from HCO3-
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11. Conversion of ribonucleotide to deoxy-
ribonucleotide
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13. Disorders of purine metabolism
 Hyperuricemia is an abnormally high level of uric acid in the blood. In the pH
conditions of body fluid, uric acid exists largely as urate.
 Daily excretion of uric acid is 500-700mg.
 Gout is a metabolic disease associated with overproduction of uric acid. At
physiological pH, uric acid is found in a more soluble form as sodium urate.
 In severe hyperuricemia, crystals of sodium urate get deposited in the soft tissue,
particularly in the joints.
 Such deposits are commonly known as tophi. This causes inflammation in the joints
resulting in a painful gouty arthritis.
 Prevalence of gout is about 3 per 1000 persons, mostly affecting males.
 Primary gout
 Inborn error of metabolism due to overproduction of uric acid.
 Increased synthesis of purine nucleotides. Lack of feedback regulation of purine
nucleotide synthesis and Lesch – nyhan syndrome result in primary gout.
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14.  Secondary gout
 Secondary hyperuricemia is due to various diseases causing increased
synthesis or decreased excretion of uric acid. Increased degradation of
nucleic acids is observed in various cancers, psoriasis, and increased tissue
breakdown.
 Treatment of gout
 Primary gout –allopurinol, this is a structural analog of hypoxanthine that
competitively inhibits the enzyme Xanthine oxidase.
 Further, allopurinol is oxidized to alloxanthine by xanthine oxidase.
 Alloxanthine in turn is a more effective inhibitor of xanthine oxidase. This
type of inhibition is referred to as suicide inhibition.
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15. Lesch-Nyhan syndrome
 Described by Michael lesch and William L. Nyhan.
 It is sex linked metabolic disorder, since the structural gene for HGPRT is
located on the X- chromosome.
 It affects only the males and is characterized by excessive uric acid
production and neurological abnormalities such as mental retardation,
aggressive behavior, learning disability.
 The patients of this disorders have an irresistible urge to bite their fingers lips
often causing self mutilation.
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17. References
 Dr.U.Satyanarayana, Dr.U.Chakrapani,2014, Essentials of
Biochemistry, Kolkata, Books and allied (p) Ltd, Page
number 202-207.
 L.Indira, K.Nagaraju, Zameer Ahmed.K,2007,first edition,
College Biochemistry-4, Bangalore, Himalaya publishing
house, Page number 92-104.
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