1. Uric Acid Metabolism & Gout

2. Polynucleotide (DNA or RNA)
Nucleic Acids
DNA
Mononucleotide
Base + Sugar + Phosphoric Acid
Base: Purine or Pyrimidine
Polynucleotide (DNA or RNA)
Mononucleotides bound by PDE bonds

3. Purine Bases (Adenine or Guanine)

4. Purine nucleotides degradation
Dietary nucleic acids (DNA & RNA)
1- Dietary DNA & RNA are degraded in the small intestine lumen to give free
purine & pyrimidine bases.
2- Purine bases are transported to intestinal mucosal cells
3- Inside intestinal mucosal cells, purine bases are catabolized into uric acid
4- Uric acid is transported to blood & finally excreted in the kidney to appear in
urine
Cellular nucleic acids (DNA & RNA)
1- DNA & RNA in cells are degraded to purine & pyrimidine nucleotides
2- Purine bases in purine nucleotides are degraded to uric acid
3- Uric acid is carried by blood to kidneys to be excreted in urine.

5. Fate of Dietary Nucleic Acids
Nucleic acids (DNA & RNA) of diet
in lumen of GIT
Purines (adenine & guanine)
ABSORBED
in intestinal mucosal cells
Uric Acid
to blood
circulation
URINE

6. Degradation of Purine Nucleotides
The end product of purine nucleotides degradation is uric acid
in primates (higher mammals including humans)
Uric acid is oxidized to allantoin (by uricase enzyme)
in mammals other than primates
Allantoin is further degraded to urea or ammonia
in animals other than mammals

7. Fate of uric acid in humans
Excessive production of uric acid causes:
Hyperuricemia : increased uric acid level in blood
(laboratory investigation)
Gout:
Clinical manifestations that appear due to hyperuricemia
that may lead to deposition of uric acid crystals in
joints & kidneys (urate crystals)
Hyperuricemia does not always cause gout

8. Gout 1- The hyperuricaemia can lead to sodium urate crystals in the
joints causing an acute then chronic gouty arthritis
leading to pain in joints with limitation of movements
especially big toe (start in small joints then to big joints)
2- Formation of uric acid stones in the kidney may be also seen
(nephrolithiasis)

10. Gouty Arthritis

11. Sodium urate crystals in urine
© 2004 John Wiley & Sons, Inc.
Voet Biochemistry 3e
Sodium urate crystals in urine

12. Causes of hyperuricemia (& Gout)
Elevation of uric acid level in blood above than 7.0 mg/dL
Uric acid level in blood is increased due to :
Underexcretion (more common)
Overproduction

13. Causes of hyperuricemia (& Gout)
1- Under excretion of uric acid (Renal causes):
Primary
Inherent excretory defect of urates
Secondary
Chronic renal disease
Lactic acidosis
Ketosis

14. Causes of hyperuricemia (& Gout)
2- Overproduction of uric acid:
Primary :
Inherited metabolic disorders in one of enzymes of purine degradation
Secondary:
1- increased nucleic acid turnover : as in cancer, chemotherapy, radiotherapy .
2- Excessive intake of purine-rich foods such as meat

15. Diagnosis of gouty arthritis
The definitive diagnosis of gouty arthritis requires aspiration and examination of synovial fluid from an affected joint (or material from a tophus) using polarized light microscopy to confirm the presence of needle-shaped monosodium urate crystals VERY IMPORTANT Hyperuricemia alone is not enough for diagnosis of gouty arthritis (i.e. not conclusive) Diagnosis is confirmed by synovial fluid aspiration

16. Monosodium urate crystals

17. Treatment of hyperuricemia & gout
Symptomatic treatment
Medications to reduce pain & inflammation (analgesics, anti-
inflammatory drugs)
Increasing uric acid excretion (uricosuric agents)
Reducing uric acid production
Allopurinol (xanthine oxidase inhibitor)
Avoidance of purine-rich food