Model Answer
0 min readIntroduction
Copper is an essential trace element vital for numerous physiological processes in the human body. It functions as a cofactor for several crucial enzymes involved in iron metabolism, neurotransmitter synthesis, antioxidant defense, and connective tissue formation. However, disruptions in copper metabolism can lead to severe health consequences, most notably Wilson’s disease, a rare autosomal recessive genetic disorder characterized by copper accumulation, particularly in the liver, brain, and cornea. Understanding the biochemical basis of both copper’s function and Wilson’s disease is critical for effective diagnosis and management.
Biochemical Role of Copper in the Body
Copper participates in a wide range of biochemical reactions, primarily as a component of various metalloenzymes. These enzymes are essential for maintaining normal physiological function.
- Ceruloplasmin: This is the major copper-carrying protein in plasma. It plays a crucial role in iron metabolism by oxidizing ferrous iron (Fe2+) to ferric iron (Fe3+), which is then bound to transferrin for transport. Approximately 95% of serum copper is bound to ceruloplasmin.
- Cytochrome c Oxidase: A vital enzyme in the electron transport chain, responsible for the final step in cellular respiration and ATP production. Copper is essential for its function.
- Superoxide Dismutase (SOD): Copper-zinc SOD (Cu/Zn SOD) is a potent antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide, protecting cells from oxidative damage.
- Lysyl Oxidase: This enzyme is involved in the cross-linking of collagen and elastin, essential for the integrity of connective tissues. Copper deficiency can lead to impaired connective tissue formation.
- Dopamine β-Hydroxylase: This enzyme catalyzes the conversion of dopamine to norepinephrine, a crucial step in neurotransmitter synthesis.
Wilson’s Disease: A Disorder of Copper Metabolism
Wilson’s disease, also known as hepatolenticular degeneration, is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene. This gene encodes a copper-transporting P-type ATPase primarily expressed in the liver. The mutation leads to impaired biliary excretion of copper, resulting in its accumulation in the liver, brain, cornea, kidneys, and other tissues.
- Pathophysiology: The accumulation of copper causes oxidative stress, leading to cellular damage and inflammation. In the liver, this can manifest as hepatitis, cirrhosis, and liver failure. In the brain, copper deposition affects the basal ganglia, causing neurological symptoms like tremors, rigidity, dysarthria, and dysphagia. Kayser-Fleischer rings (copper deposits in the cornea) are a characteristic clinical sign.
- Genetic Basis: Over 300 different mutations in the ATP7B gene have been identified, leading to varying degrees of severity of the disease.
- Clinical Manifestations: Symptoms typically appear between the ages of 5 and 35, but can present earlier or later. The presentation is highly variable, ranging from primarily hepatic disease to predominantly neurological or psychiatric symptoms.
Biochemical Investigations for Diagnosis
Diagnosing Wilson’s disease requires a combination of clinical evaluation and biochemical investigations. The following tests are commonly used:
- Serum Ceruloplasmin: Levels are typically low (<20 mg/dL) in Wilson’s disease, but this is not always definitive as levels can be affected by other conditions (e.g., malnutrition, nephrotic syndrome).
- 24-Hour Urinary Copper Excretion: Significantly elevated (>100 µg/day) in untreated Wilson’s disease. This is a more sensitive indicator than serum ceruloplasmin.
- Hepatic Copper Content: A liver biopsy is performed to measure the copper concentration. A hepatic copper content >250 µg/g dry weight is diagnostic of Wilson’s disease.
- Slit-Lamp Examination: To detect Kayser-Fleischer rings, which are highly suggestive of the disease.
- Genetic Testing: Mutation analysis of the ATP7B gene can confirm the diagnosis, but is not always necessary if clinical and biochemical findings are conclusive.
| Investigation | Typical Findings in Wilson’s Disease |
|---|---|
| Serum Ceruloplasmin | Low (<20 mg/dL) |
| 24-Hour Urinary Copper | High (>100 µg/day) |
| Hepatic Copper Content | High (>250 µg/g dry weight) |
| Kayser-Fleischer Rings | Present |
Conclusion
Copper is an indispensable element involved in numerous vital biochemical processes. Wilson’s disease, a consequence of impaired copper metabolism, highlights the importance of maintaining copper homeostasis. Accurate diagnosis relies on a combination of clinical assessment and biochemical investigations, including ceruloplasmin levels, urinary copper excretion, and hepatic copper content. Early diagnosis and treatment are crucial to prevent irreversible organ damage and improve the quality of life for affected individuals.
Answer Length
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