Question

What are the sources of propionyl-CoA in methylmalonic acidemia?

Answer 1

Methylmalonic acidemia is a occasional autosomal recessive genetic disorder.

The condition is resulted due to body's inability to absorb certain proteins and fats (lipids) properly.

The disorder usually observed in early beginning. The disorder is a type of organic acidemia resulting in buildup of a toxic level of methylmalonic acid in the blood.

The condition arises due to fault of the enzyme methylmalonyl-CoA mutase that converts methylmalonyl-coenzyme A (CoA) into succinyl-CoA.

The enzyme methylmalonyl-CoA mutase requires vitamin B₁₂ as cofactor. Insufficient levels of vitamin B₁₂ cause the build up of methylmalonic acid. In methylmalonic acidemia, the body is unable to metabolize the amino acids methionine, threonine, isoleucine and valine. T

he enzyme propionyl-CoA carboxylase converts propionyl-CoA to methylmalonyl-CoA.

The essential amino acids valine, methionine, isoleucine, and threonine, and other odd-chain fatty acids are simply converted to propionyl-CoA and are the sources of propionyl-CoA in methylmalonic acidemia. Accumulation of organic acids result in hypoglycemia, build up of ketones resulting in ketosis, inhibition of urea cycle causing hyperammonenia and neutropenia etc.

Symptoms of disorder:

The symptoms include vomiting, dehydration, weak muscle tone or hypotonia, slow developmental, excessive tiredness or lethargy, hepatomegaly, and failure to gain weight. Long-term complications may include feeding problems, intellectual disability, chronic kidney disease, and inflammation of the pancreas or pancreatitis.

The condition can be fatal without treatment and the disorder can lead to coma and death