BIOCHEMISTRY ON CATABOLISM OF PURINE NUCLEOTIDES

1. BIOCHEMISTRY
On
CATABOLISM OF PURINE NUCLEOTIDES
presented by:
Pawde Laxman
B.Pharm 1St year
Nanded Pharmacy College
Mentor:
Mulay mam
lect. At- Nanded Pharmacy College
9/08/2019

2. Content
A. Catabolism Of Purine Nucleotides
B. Uric Acid
C. Disorders of Purine Metabolism
i)Gout
ii)Hyperuricemia

3. Catabolism Of Purine Nucleotides
 The nucleotide monophosphate (AMP,IMP,GMP) are converted to
their respective nucleotides from (Adenosine,Inosine,Guanosine) by
the action of nucleotide.
 The amino group , either from AMP or Adenosine , can be
removed to produce IMP or Inosine respectively.
 Inosine and Guanosine are respectively converted to Hypoxanthine
and Guanine (purine bases) by purine nucleoside phosphorylase .
Adenosine is not degraded by this enzyme , hence it has to be
converted to inosine.

5.  Guanine undergoes deamination by guanase to from xanthine.
 Xanthine oxidase is an important enzyme that converts
hypoxanthine to xanthine and xanthine to uric acid.
 This enzyme contain FAD , molybdenum and iron and is
exclusively found in liver and small intestine.
 Xanthine oxidase liberates H2O2 which is harmful to the tissues .
Catalase cleaves H2O2 to H2O & O2

6.  URIC ACID (2,6,8 – trioxypurine)
 It is First excretory product of purine metabolism in humans.
 Uric acid can serve as an important antioxidant by getting itself
converted(non-enzymatically) to allontoin.
 It is believed that antioxidant role of ascorbic acid in primates is
replaced by Uric acid , since this animals have lost the ability to
synthesize ascorbic acids.
 Most animals (other than primates) however, oxidise uric acid by
enzyme uricase to allontoin , where the purine ring is cleaved .

7. URIC ACID

8.  Allontoin is then converted to allontoic acid excreted in some
fishes .
 Further degradation of allontoic acid may occur to produce
urea (in amphibians,most fishes and some molluscs) and later ,
to ammonia (in marine invertebrates).

9. Disorders Of Purine Metabolism
Gout
 Gout is the metabolic disease associated with overproduction of
uric acid.
 At the physiological pH , Uric acid is found in more soluble form
as sodium urate.
 Sodium urate or uric acid may also participate in kidneys and
ureters that results in renal damage and stone formation.
 Historically gout was found to be often associated with high
living , over eating and alcohol consumption.

10. GOUT

11.  In previous centuries , alcohol was contaminated with lead during
its manufacture and storage.
 Lead poisoing leads to kidney damage and decreased uric acid
excretion causing gout.
 In general , a rich diet is meat and seafoods is associated with
increased risk of gout.
 The prevalence of gout is about 3 per 1000 persons , mostly
affecting males.
 Post-menopausal woman , however are as susceptible as men for
this disease.
 Gout is of two types  i) primary and ii) secondary

12. Primary Gout
 It is inborn error of metabolism due to overproduction of uric
acid.
 This is mostly related to increased synthesis of purine
nucleotides.
 The following are the important metabolic defects (enzymes)
associated with primary gout
I) PRPP Synthetase
II) PRPP glutamylamidotransferase
III) HGPRT defiency
IV) Glucose-6-phosphate deficiency
V) Elevation of glutathione reductase

13.  Among the five enzymes described , the first three are directly
involved in purine synthesis.
 The remaining two are indirectly regulate purine production .

14. Secondary Gout
 Secondary hyperuricemia is due to various diseases causing
increased synthesis or decreased excretion of uric acid
 Increased degradation of nucleic acids (more uric acid
formation) is observed in various Cancers
(leukemia,lymphomas), psoriasis and increased tissue
breakdown(trauma, starvation ,etc).

15. Treatment Of Gout
 The drug choice for the treatment of primary gout is
allopurinol.
 This is structural analog of hypoxanthine that competitively
inhibits the enzyme xanthine oxidase.
 Further , allopurinol is oxidised to alloxanthine by xanthine
oxidase.
 Alloxanthine , in turn , is a more effective inhibitor of
xanthine oxidase.
 Besides the drug therapy, restriction in dietary intake of
purines and alcohol is advised .

16.  Consumption of plenty of water is useful.
 The anti-inflammatory drug colchicine is used for the
treatment of gouty arthritis .
 Other anti-inflammatory drugs – such as phenylbutazone ,
indomethacin , oxyphenbutazone, corticosteroids are also
useful.

17. Hyperuricemia
 Hyperuricemia refers to elevation in serum uric acid
concentration.
 This is sometimes associated with increased uric acid
excretion(uricosuria).
 In severe hyperuricemia , crystals of sodium urate get
deposited in the soft tissues , particularly at the joints. such
deposits are commonly known as Tophi.

18. HYPERURICEMIA

19. Reference
1) Biochemistry – U.Satyanarayana &
U.Chakrapani (page no. 393)
2) Biochemistry – Pee Vee publication (page no.
290)
3) Biochemistry – Nirali Publication (Content – 7.11)