Loading tests, metabolic valine

Methylmalonyl-CoA mutase is a cobalamin-linked enzyme of mitochondria that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. A reduction of this enzyme due to vitamin B12 deficiency will result in a metabolic block with the urinary excretion of methylmalonic acid, and the measurement of this metabolite has been used to confirm a deficiency of vitamin B12. The test has also been useful in investigating rare abnormalities of this enzyme that result in the excretion of methylmalonic acid in the presence of adequate vitamin B12. Given an oral loading dose of valine or isoleucine will increase the urinary excretion of methylmalonic acid in patients with a vitamin B12 deficiency (G4). However, Chanarin and his colleagues (CIO) found that one-quarter of their patients with pernicious anemia excreted a normal concentration of methylmalonic acid even after a loading dose of valine. Normal subjects excrete up to 15 mg of methylmalonic acid in their urine over a 24-hour period (Cll). 

A test which can be used in the investigation of vitamin Bj2 deficiency. The metabolism of valine contains a step in which methylmalonyl coenzyme A is converted to succinyl coenzyme A, an enzymic reaction which requires vitamin B12 as a cofactor. In vitamin B deficient individuals, administration of an oral load of valine results in a greater than normal excretion of methylmalonate in the urine which can be estimated colorimetrically. 

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