This PPT contains topic on Catabolism of purine nucleotides, Hyperuricemia and Gout. Book referred: https://www.amazon.in/BIOCHEMISTRY-SATYANARAYANA-5TH-2017/dp/B073Y7XGH4

2. Degradation of purine nucleotides
• End product of purine metabolism: Uric Acid.
• The sequence of reactions in purine
nucleotide degradation is described in thenucleotide degradation is described in the
upcoming slide

3. Step 1
• Nucleotide monophosphates are converted to
nucleoside forms by nucleotidase.
– AMP  Adenosine– AMP  Adenosine
– IMP  Inosine
– GMP  Guanosine

4. Step 2
• The amino group are removed.
– Amino group removed from AMP to produce IMP.
– Amino group removed from adenosine to produce– Amino group removed from adenosine to produce
inosine.

5. Step 3
• Inosine  Hypoxanthine by “Purine
nucleoside phosphorylase”
• Guanosine  Guanine by “Purine nucleoside• Guanosine  Guanine by “Purine nucleoside
phosphorylase”

6. Step 4
• Guanine  Xanthine by “Guanase”
• Deamination reaction

7. Step 5
• Hypoxanthine  Xanthine  Uric acid by
“Xanthine oxidase”.
• Xanthine oxidase is an important enzyme which
catalyses both reactions.
Xanthine oxidase is an important enzyme which
catalyses both reactions.
• Xanthine oxidase liberates H2O2 which is harmful
to the tissues. Catalase cleaves H2O2 to H2O and
O2.

8. AMP IMP GMP
Adenosine Inosine Guanosine
HypoxanthineHypoxanthine
Xanthine
Uric acid
Guanine

9. • Uric acid (2,6,8-trioxypurine) is the final
excretory product of purine metabolism in
humans.
• It is an important antioxidant, which converts
itself to Allantoin.itself to Allantoin.
• Antioxidant role of ascorbic acid in primates is
replaced by uric acid, since these animals have
lost the ability to synthesize ascorbic acid.

10. Hyperuricemia and Gout disease
• Uric acid normal concentration in the serum of adults is
in the range of 3-7 mg/dl.
• The daily excretion of uric acid is about 500-700 mg.
• Hyperuricemia refers to an elevation in the serum uric• Hyperuricemia refers to an elevation in the serum uric
acid concentration, sometimes associated with increased
uric acid excretion (uricosuria).
• Gout is a metabolic disease associated with
overproduction of uric acid.

11. Gout types
• Primary
• Secondary

12. Primary Gout
Inborn error of metabolism due to overproduction of uric acid,
mostly related to increased synthesis of purine nucleotides.
The following are the important metabolic defects (enzymes)
associated with primary gout:
● PRPP synthetase : PRPP synthetase is under feedback control by● PRPP synthetase : PRPP synthetase is under feedback control by
purine nucleotides (ADP and GDP). But variant forms of PRPP
synthetase, (not subjected to feedback regulation) have been
detected. This leads to the increased production of purines.
● PRPP glutamylamidotransferase : The lack of feedback control
of this enzyme by purine nucleotides also leads to their
elevated synthesis.

13. 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.
– Decreased utilization of purines (hypoxanthine and
guanine) by salvage pathway, resulting in the accumulationguanine) 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 GMP causing impairment in the tightly
controlled feedback regulation of their production.

14. ● Glucose 6-phosphatase deficiency : Due to the
deficiency of glucose 6-phosphatase, glucose 6-
phosphate cannot be converted to glucose in type I
glycogen storage disease (von Gierke’s).
This leads to the increased utilization of glucose 6-
phosphate by HMP shunt, resulting in elevated levels
of ribose 5-phosphate and PRPP and, ultimately, purineof ribose 5-phosphate and PRPP and, ultimately, purine
overproduction.
In von Gierke’s disease there is increased activity of
glycolysis. Due to this, lactic acid is accumulated in the
body interfering the uric acid excretion.

15. • Elevation of glutathione reductase : Increased
glutathione reductase generates more NADP+
which is utilized by HMP shunt. This causes
increased ribose 5-phosphate and PRPP
synthesis.synthesis.

16. 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, psoriasis
Increased degradation of nucleic acids (hence more uric
acid formation) is observed in various cancers, psoriasis
and increased tissue breakdown.
The disorders associated with impairment in renal
function cause accumulation of uric acid which may
lead to gout.