The final product of methylmalonyl-CoA mutase activity is succinyl-CoA which is a tricarboxylic acid cycle substrate.
A side effect of excess methylmalonyl-CoA is an interruption of the enzymes responsible for other transformations earlier in the metabolism of propionyl-CoA, leading to propanoic acidemia as well.
This, along with an excess of methylmalonyl-CoA leads to the depletion of ATP through oxidative stress and coenzyme A. This disrupts the biosynthesis of myelin, urea, and glucose.
Specifically, excess methylmalonyl-CoA places oxidative stress on the mitochondrial enzymes involved in the urea cycle (such as ammonia-dependent-carbamoyl-phosphate synthase or CPS1), and inhibits its mechanism of action.
The combination of inhibited urea synthesis and poor protein metabolism, as well as a weakly replenished tricarboxylic acid cycle contribute to the symptoms of methylmalonic acidemia.
The final product of methylmalonyl-CoA mutase activity is succinyl-CoA which is a tricarboxylic acid cycle substrate. A side effect of excess methylmalonyl-CoA is an interruption of the enzymes responsible for other transformations earlier in the metabolism of propionyl-CoA, leading to propanoic acidemia as well. This, along with an excess of methylmalonyl-CoA leads to the depletion of ATP through oxidative stress and coenzyme A. This disrupts the biosynthesis of myelin, urea, and glucose. Specifically, excess methylmalonyl-CoA places oxidative stress on the mitochondrial enzymes involved in the urea cycle (such as ammonia-dependent-carbamoyl-phosphate synthase or CPS1), and inhibits its mechanism of action. The combination of inhibited urea synthesis and poor protein metabolism, as well as a weakly replenished tricarboxylic acid cycle contribute to the symptoms of methylmalonic acidemia.
Methylmalonyl-CoA mutase deficiency