Blood and Body Fluids: Purine Catabolism

Course Information

• Faculty of Medicine
• Academic Year: 2024-2025
• Year: 1
• Semester: 1
• Module: Blood and Body Fluids (BLF) 103

Purine Catabolism & Gout

• Topic: Purine Catabolism & Gout
• Lecturer: Dr. Marwa Ali
• Department: Medical Biochemistry and Molecular Biology
• University: Ain Shams University
• Objectives:
  • Illustrate the steps of purine catabolism.
  • Demonstrate the causes of hyperuricemia.
  • Interpret the biochemical basis of gout and its treatment.
  • Correlate purine metabolism with immune diseases.

Purines and Pyrimidines

• Structures of purines (adenine, guanine) and pyrimidines (cytosine, uracil, thymine) are shown.
• Purines are shown with specific numbering of atoms.
• Pyrimidines are also shown with specific numbering of atoms.
• Adenine and guanine are purines.
• Cytosine, uracil, and thymine are pyrimidines.
• Uracil is found in RNA
• Thymine is found in DNA

Catabolism of Purine Nucleotides

• Dietary purine nucleotides are degraded into uric acid in intestinal mucosal cells.
• Cellular nucleic acids are broken down after cell death or unstable RNA degradation.
• Uric acid is the final product in human purine degradation and excreted in urine.
• 2,6,8 tri-oxy-purine is a structure of uric acid.

Purine Metabolism Pathway

• A detailed pathway diagram (chemical equations) shows the breakdown of purine nucleotides (with names of enzymes).
• The pathway details the steps leading from purine nucleotides to uric acid.

Normal Serum Uric Acid Levels

• Male: 3-7 mg/dL
• Female: 2-6 mg/dL
• Exceeding normal levels signifies hyperuricemia.

Gout

• Gout is a disorder characterized by high uric acid levels.
• Causes of gout include under-excretion and over-production of uric acid.

Under-excretion of Uric Acid

• Inherited excretory defect of the kidney is a primary cause.
• Excessive ethanol consumption lowers uric acid excretion.

Over-production of Uric Acid

• Primary: Defects in enzymes of purine synthesis.
  • Genetic defect of PRPP synthetase leads to excess purine synthesis.
  • Lesch-Nyhan syndrome (HGPRT gene defect) is a genetic disorder leading to the inability to reuse purines, which are degraded into uric acid.
• Secondary: Causes outside purine synthesis pathway.
  • Increased nucleic acids in the diet (e.g., high-purine foods).
  • Increased cellular breakdown in conditions like malignancies and the use of anticancer drugs.
  • Genetic diseases such as von Gierke disease (glucose-6-phosphatase deficiency).

Lesch-Nyhan Syndrome Symptoms

• Abnormally elevated uric acid levels
• Mental retardation
• Neurological symptoms
• Self-mutilating behaviors (lip and finger biting, head banging)
• Orange-colored deposits ("orange sand") in infant diapers is an early indicator.

Gout Clinical Picture

• Gout can cause crystal deposition in joints, kidneys, and soft tissues.
• Joints: Deposition of needle-shaped urate crystals, leading to severe inflammation (gouty arthritis).
• Typically affects the big toe joint first, but other joints can also be affected (e.g., feet, ankles, knees, wrists, fingers, elbows).
• Acute attacks happen with fever and swollen, red, and painful joints.
• Kidneys: Uric acid stones.
• Soft Tissues: Tophi (nodular masses of sodium urate crystals) below the skin.

Gout Treatment

• Acute Attacks: Rapid pain relief using analgesics and anti-inflammatory medications (e.g., cholchicine, NSAIDs) to reduce granulocyte movement.
• Long-term Therapy: Xanthine oxidase inhibitors (allopurinol) to decrease uric acid production and accumulation.
• Dietary Therapy: Avoid foods rich in purines (e.g., red meat, liver, peas, beans, lentils, beer, alcohol, coffee). Increase fluids to increase uric acid elimination. Include fruits in diet (fruits have few purines)
• Alkalinization of Urine: Increase urine alkalinity to increase the solubility of uric acid.

Adenosine Deaminase Deficiency (ADA)

• ADA converts adenosine to inosine.
• ADA deficiency prevents DNA production and cell division.
• Severe combined immune deficiency (SCID) is a symptom if ADA deficiency.

Purine Nucleoside Phosphorylase (PNP) Deficiency

• PNP deficiency is less common and less severe than ADA deficiency.
• Only T-cells are affected.
• Symptoms include recurrent infections and neurodevelopmental delays.

Additional Points

• Different types of gout.
• Investigating diagnosis of gout.

This quiz covers the essential concepts of purine catabolism and its relation to gout. You will explore the biochemical pathways involved, understand the causes of hyperuricemia, and discuss treatment options for gout. Test your knowledge on purines and pyrimidines as you relate them to immune diseases.