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1. BIOCHEMISTRY
[B. Pharm – I Yr.]
Topic: Biosynthesis and Catabolism of Purine Nucleotides
Umesh Kumar
Assistant Professor
Dept. of Pharm. Chemistry
Hygia Institute of Pharmaceutical Education and Research

2. CONTENTS
• Biosynthesis of Purine nucleotides
• Introduction
• Biosynthesis of prine nucleotides
• Catabolism of Purine nucleotides
• Disorders of Purine nucleotides

3. Nucleotides
• Nucleotides consist of a nitrogenous base, a pentose and a phosphate.
• The pentose sugar is D-ribose in ribonucleotides of RNA while in deoxyribonucleotides
(deoxynucleotides) of DNA, the sugar is 2-deoxy D-ribose.
• Nucleotides participate in almost all the biochemical processes either directly or indirectly.
• They are the structural components of nucleic acids (DNA, RNA), coenzymes, and are involved in
the regulation of several metabolic reactions

4. • The structures of major purines and pyrimidines
found in nucleic acids are shown in the following
image.
• DNA and RNA contain the same purines namely
adenine (A) and guanine (G), Further, the
pyrimidine cytosine (C) is found in both DNA and
RNA.
• However, the nucleic acids differ with respect to
the second pyrimidine base. DNA contains
thymine (T) whereas RNA contains uracil (U).
• As is observed in the Fig,5.2, thymine and uracil
differ in structure by the presence (in T) or
absence (in U) of a methyl group.
Purines and Pyrimidines

5. Biosynthesis of Purine Nucleotides
• It should be remembered that purine bases are not synthesized as such, but they are formed as
ribonucleotides.
• The purines are built upon a pre-existing ribose-5-phosphate.
• Liver is the major site for purine nucleotide synthesis.
• Erythrocytes, polymorphonuclear leukocytes and brain cannot produce purines.
• Generally, pathway takes place for the synthesis of Inosine Monophosphate which is the parent
nucleotide of purine nucleotides.
• For the synthesis of inosine monophosphate, the reaction takes place in total 11 steps.

8. SynthesisofAMPand GMPfromIMP

9. Salvage Pathway for Purines
• The free purines (adenine, guanine and hypoxanthine) are formed in the normal turnover of nucleic
acids (particularly RNA), and also obtained from the dietary sources.
• The purines can be directly converted to the corresponding nucleotides, and this process is known as
'salvage pathway’.

10. • Uric acid is the final excretory product of purine metabolismin humans.
• Uric acid can serve as an important antioxidant by getting itself converted to allatonin.
Catabolism of Purine Nucleotides

12. Disorders of Purine Metabolism
Hiperuricemia and Gout
• Uric acid is the end product of purine metabolism in humans.
• The normal concentration of uric acid in the serum of adults is in the range of 3-7 mg/dl.
• In women, it is slightly lower (by about 1 mg) than in men. The daily excretion of uric acid is about
500-700 mg.
• Hyperuricemia refers to an elevation in the serum uric acid concentration. This is sometimes
associated with increased uric acid excretion (uricosuria).
• Gout is a metabolic disease associated with overproduction of uric acid.
• At the physiological pH, uric acid is found in a more soluble form as sodium urate.
• ln severe hyperuricemia, crystals of sodium urate get deposited in the soft tissues, particularly in the
joints.
• Such deposits are commonly known as tophi. This causes inflammation in the joints resulting in a
painful gouty arthritis.
• Sodium urate and/or uric acid may also precipitate in kidneys and ureters that results in renal damage
and stone formation.

14. • Historically, gout was found to be often associated with high living, over-eating and alcohol
consumption.
• In the previous centuries, alcohol was contaminated with lead during its manufacture and storage.
• Lead poisoning leads to kidney damage and decreased uric acid excretion causing gout.
• Gout is of two types –
1. Primary Gout
2. Secondary Gout
Primary Gout
• It is an 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-
• PRPP synthetase
• PRPP glutamylamidotransferase
• HGPRT deficiency

15. HGPRT deficiency
• This is an enzyme of purine salvage pathway, and its defect causes Lesch-Nyhan syndrome.
• This disorder is associated with increased synthesis of purine nucleotides by a two-fold
mechanism.
• Firstly, decreased utilization of purines (hypoxanthine and guanine) by salvage pathway, resulting
in the accumulation and diversion of PRPP for purine nucleotides.
• Secondly, the defect in salvage pathway leads to decreased levels of IMP and CMP causing
impairment in the tightly controlled feedback regulation of their production.
Secondary gout
• Secondary hyperuricemia is due to various diseases causing 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.).
• The disorders associated with impairment in renal function cause accumulation of uric acid which
may lead to gout.

17. THANK YOU
HYGIA GROUP OF INSTITUTIONS
GHAILA ROAD, GAAZIPUR BALRAM,
FAIZULLAHGANJ, LUCKNOW