This document summarizes purine biosynthesis and degradation. Purine is synthesized through an 11 step pathway forming IMP, the parent nucleotide. IMP is then used to synthesize AMP and GMP. Purines are broken down to uric acid through a multi-step process. Gout is caused by excessive uric acid formation due to increased purine biosynthesis or decreased excretion leading to uric acid crystal deposition in joints.

1. welcome

2. Biosynthesis and degradation of
purine
M.sridevi
M.Sc. microbiology

3. Introduction
 Purine is a heterocyclic aromatic organic
compound that consists of a pyrimidine ring
fused to an imidazole ring.
 Purine is water soluble.
 Purine are found in high concentration in meat &
meat products , especially internal organ such as
liver & kidney.

4. Properties
 Purine is both a very weak acid and even weaker
base.
 There are many naturally occurring purine .
 They include the nucleobases
 adenine
Guanine
 Other notable purines are hypoxanthine , xanthine,
Theo bromine , caffeine , uric acid , isoguanine .

5. purine metabolism
 Purine metabolism refer to the metabolic
pathway to synthesize & breakdown purine that
are present in many organism .
 Purine are biologically synthesized as
nucleotides.
 Both adenine and guanine are derived from the
nucleotide inosine monophosphate (IMP) or
inosinic acid

6. The synthesis of IMP
IMP is synthesized in a pathway composed of 11 reactions.
• Activation of ribose – 5 – phosphate
• Acquisition of purine atom N9
• Acquisition of purine atom C4,C5 & N7
• Acquisition of purine atom C8
• Acquisition of purine atom N3
• Formation of the purine imidazole ring
• Acquisition of C6
• Acquisition of N1
• Elimination of fumarate
• Acquisition of C2
• Cyclization to form IMP

7. Cont…
Step 1 :
• Ribose 5- phosphate is the starting material
for purine nucleotide synthesis .
• It react with ATP to form phosporibosyl
pyrophosphate (PRPP).
Step 2 :
• Glutamine transfer its amide nitrogen to
PRPP to replace pyrophosphate and produce 5
–phosphoribosylamine .

8. Step 3 :
• Phosphoribosylamine reacts with glycine
in the presence of ATP to form
glycinamide ribosyl 5 –phosphate (or)
glycinamide ribotide (GAR).
Step 4 :
• N10 –formyl tetrahydrofolate donates the
formyl group & the product formed is
formyl glycinamide ribosyl 5-phosphate.

9. Step 5 :
• Glutamine transfer the second amido amino
group to produce formylglycinamidine ribosyl 5-
phosphate .
Step 6 :
• The imidazole ring of the purine is closed in an
ATP dependent reaction to yield 5-amino
imidazole ribosyl 5-phosphate .
Step 7 :
• Incorporation of co2 occurs to yield
aminoimidazole carboxylate ribosyl 5-phosphate
.

10. Step8:
•Aspartate condenses with the product
in reaction 7 to form aminoimidazole 4
succinyl carboxamide ribosyl 5-
phosphate.
Step9:
•Adenosuccinate lyase cleaves off
fumarate and only the amino group of
aspartate is retained to yield
aminoimidazole 4-carboxamide ribosyl
5-phosphate.

11. Step 10:
• N 10- formyl tetrahydrofolate donates a one – carbon
moiety to produce formaminoimidazole 4 carboxamide
ribosyl 5 phosphate.
Step11:
• The final reaction catalysed by cyclohydrase leads to ring
closure with an elimination of water molecule. The product
obtained is inosine monophosphate (IMP), the parent
purine nucleotide from which other purine nucleotides can
be synthesized.

15. Synthesis of AMP and GMP from IMP
For the synthesis of GMP , IMP undergoes
NAD + dependent dehydrogenation to form
xanthosine monophosphate (XMP) .
Glutamine then transfer amide nitrogen to
XMP to produce GMP.
Aspartate condenses with IMP in the
presence GTP to produce adenylsuccinate
which , on cleavage , forms AMP .

17. Degradation of purine nucleotide
The end product of purine metabolism in
human is uric acid .
Uric acid can serve as an important
antioxidant .
The normal concentration of uric acid in the
serum of adults is in the range of 3 -7 mg/dl

18. Cont….
Step 1 :
• The nucleotide monophosphate (AMP, IMP
& GMP) are converted to their respective
nucleoside forms (adenosine , inosine &
guanosine ) by the action of nucleotidase.
Step 2 :
• The amino group , either from AMP or
adenosine , can be removed to produce
IMP or inosine .

19. Step 3:
• Inosine and guanosine are , respectively ,
converted to hypoxanthine and guanine by
purine nucleoside phosporylase .
Step 4:
• Guanine undergoes deamination by guanase to
form xanthine.
Step 5:
• Xanthine oxidase is an important enzyme that
convert hypoxanthine to xanthine , &
xanthine to uric acid.

21. Disorder of purine metabolism
 Gout is a genetic disorder of purine catabolism.
 It is caused by excessive formation of uric acid
due to increased purine biosynthesis .
 Two characteristic features in gout are ,
Hyperuricemia
Uricosuria

22. Gout
 Characterized by hyperuricemia and acute arthritic joint
inflammation by deposition of uric acid crystals
 Primary gout is genetic and mainly affects men over 30
 Secondary gout is associated with leukemia, polycythemia,
HGPRT deficiency, renal insufficiency, lifestyle (rich foods)