The enzyme affected in Menkes disease is a copper-transporting ATPase known as ATP7A. This enzyme is crucial for the proper distribution of copper throughout the body.
Understanding ATP7A and Menkes Disease
Menkes disease, also known as Menkes syndrome, is a genetic disorder resulting from mutations in the ATP7A gene. This gene provides instructions for making the ATP7A protein, which, as mentioned above, is a copper-transporting ATPase. The ATP7A protein is primarily found in the membrane of cells and is responsible for moving copper across cell membranes.
The Role of ATP7A in Copper Transport
ATP7A plays a critical role in two main functions:
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Copper Absorption: In the small intestine, ATP7A helps absorb copper from the diet.
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Copper Delivery: In other cells throughout the body, ATP7A transports copper to enzymes that require it as a cofactor for their function. These copper-dependent enzymes are essential for various processes, including:
- Ceruloplasmin synthesis: Ceruloplasmin is involved in iron metabolism.
- Lysyl oxidase activity: Lysyl oxidase is necessary for collagen and elastin formation. This enzyme is responsible for cross-linking collagen and elastin, which are critical for the structure and strength of connective tissue.
- Dopamine beta-hydroxylase function: Dopamine beta-hydroxylase is needed for neurotransmitter production (norepinephrine and epinephrine).
- Cytochrome c oxidase activity: Cytochrome c oxidase is essential for energy production in mitochondria.
- Tyrosinase Activity: Tyrosinase is required for melanin synthesis (skin and hair pigmentation).
Consequences of ATP7A Dysfunction
When the ATP7A gene is mutated, the ATP7A protein is either non-functional or absent. This leads to impaired copper transport, resulting in:
- Copper deficiency in most tissues: Cells cannot efficiently acquire the copper they need.
- Copper accumulation in the small intestine and some other tissues: Copper gets trapped where it should be transported away from.
The systemic copper deficiency, in turn, impairs the function of the copper-dependent enzymes, leading to the various symptoms associated with Menkes disease, such as:
- Neurological problems (seizures, developmental delays)
- Kinky hair (pili torti)
- Skeletal abnormalities
- Failure to thrive
In summary:
The Menkes disease enzyme is the copper-transporting ATPase, ATP7A. Mutations in the ATP7A gene cause Menkes disease by disrupting proper copper distribution throughout the body.
