Uric Acid Metabolism and Transport

Uric Acid Metabolism

• Uric acid is the final breakdown product of purine metabolism (adenosine/guanine) in the liver.
• 70% of uric acid is transported to the kidney and filtered, with 98% reabsorbed in the proximal convoluted tubule (PCT).
• 6-12% of the filtered amount is secreted by the distal convoluted tubule (DCT).
• The remaining 30% is eliminated through the gastrointestinal tract (GIT).

Biochemistry

• Uric acid has a molecular formula of C5H4N4O3 and a molecular weight of 168.
• Humans lack the enzyme uricase, which converts uric acid into the more soluble compound allantoin, unlike most other mammals.
• Purine bases, including adenine and guanine, are present in DNA and RNA and are derived from:
  • Breakdown of ingested meat containing nucleic acid.
  • Synthesis from small molecules.

Renal Excretion

• Uric acid is transported through the plasma to the kidney, where it is filtered by the glomerulus.
• Most uric acid in plasma is present as monosodium urate, which is insoluble in water.
• Renal excretion of uric acid involves four pathways: filtration, reabsorption, secretion, and post-secretary reabsorption.

Clinical Applications

• Uric acid measurement is used to:
  • Assess inherited disorders of purine metabolism.
  • Confirm diagnosis and monitor treatment of gout.
  • Assist in the diagnosis of renal calculi.
  • Prevent uric acid nephropathy during chemotherapeutic treatment.

Abnormalities of Uric Acid

Hyperuricemia

• Defined as a high level of serum uric acid (> upper normal range).
• Mainly affects men.
• Causes:
  • Overproduction of uric acid in 25-30% of cases.
  • Increased catabolism of nucleic acids.
  • Chronic renal disease, which impairs filtration and secretion.
• Effects:
  • Pain and inflammation of joints due to sodium urate precipitation in tissues.
  • Increased risk of renal calculi.

Hypouricemia

• Defined as a low level of serum uric acid (< lower normal range).
• Less common than hyperuricemia.
• Causes:
  • Severe liver disease.
  • Defective renal tubular reabsorption.
  • Chemotherapy with 6-mercaptopurine, which inhibits purine synthesis.
  • Over-treatment with allopurinol.

Analytical Methods

• Primary method uses enzyme uricase (urate oxidase) to convert uric acid to allantoin.
• Differential absorption at 293 nm, where uric acid has a UV absorbance peak.
• Newer methods couple uricase with catalase or peroxidase action on hydrogen peroxide product from allantoin production.

Gout

• A disease primarily affecting men between 30 and 50 years of age.
• Characterized by pain and inflammation of joints due to sodium urate precipitation.
• Classified into two categories:
  • Primary gout: defect in urate metabolism (lack of enzyme).
  • Secondary gout: due to other factors.