Blood and Body Fluids: Purine Catabolism

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Questions and Answers

What is a primary cause of overproduction of uric acid in gout?

Treatment with steroids

Inability to break down glucose-6-phosphate

Increased nucleic acids from a high-carb diet

Genetic defect in PRPP synthetase (correct)

Which option describes the characteristic symptom of Lesch-Nyhan syndrome?

Persistent headache and fatigue

Increased uric acid and self-mutilating behaviors (correct)

Weakness and muscle cramps

Chronic cough and sore throat

What is the final product of human purine degradation excreted in urine?

Uric acid (correct)

Guanine

Hypoxanthine

Xanthine

In gout, where are needle-shaped sodium urate crystals typically deposited?

Joints and kidneys Signup and view all the answers

What is the primary cause of hyperuricemia in most patients with gout?

Inherited excretory defect of the kidney Signup and view all the answers

What dietary factor may lead to secondary gout?

Excessive meat intake Signup and view all the answers

What is the primary goal during acute attacks of gout?

Achieve rapid pain relief Signup and view all the answers

Which enzyme is responsible for converting xanthine to uric acid?

Xanthine oxidase Signup and view all the answers

In females, what is the normal serum uric acid level range?

2-6 mg/dl Signup and view all the answers

Which factor does NOT contribute to under-excretion of uric acid?

Increased physical activity Signup and view all the answers

What is the main action of allopurinol in the management of chronic gout?

It inhibits the formation of uric acid. Signup and view all the answers

Which dietary changes are recommended to prevent future gout attacks?

Consume plenty of fruits and stay hydrated. Signup and view all the answers

What metabolic pathway is primarily associated with the overproduction of uric acid in gout?

De novo purine biosynthesis. Signup and view all the answers

In patients with adenosine deaminase deficiency, what is the primary consequence of this enzyme's deficiency?

Impaired DNA synthesis and cell division. Signup and view all the answers

What does alkalinization of urine aim to achieve in the management of gout?

Increase solubility of uric acid. Signup and view all the answers

Why are patients advised to avoid beer and alcoholic beverages in gout management?

They increase uric acid production. Signup and view all the answers

Which condition is best described by the symptoms of pneumonia, chronic diarrhea, and developmental delay due to purine metabolism issues?

Adenosine deaminase deficiency. Signup and view all the answers

In the context of gout management, which of the following is not an effect of cholchicine?

Reduces uric acid production. Signup and view all the answers

What is the primary characteristic of purine nucleoside phosphorylase deficiency compared to adenosine deaminase deficiency?

It predominantly results in recurrent infections. Signup and view all the answers

What is the role of xanthine oxidase in uric acid metabolism?

It catalyzes the conversion of hypoxanthine to uric acid. Signup and view all the answers

Study Notes

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.

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Description

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.