What does methylmalonyl-CoA inhibit?
Human methylmalonyl-CoA mutase is inhibited by ethylmalonyl-CoA, cyclopropylcarbonyl-CoA carboxylate, and methylenecyclopropylacetyl-CoA, which are substrate, intermediate, and product analogs, respectively. The mode of inhibition by each analog is reversible and mixed with respect to the substrate, methylmalonyl-CoA.
What is Methylmalonyl-CoA Mutase deficiency?
Methylmalonyl-Coenzyme A mutase deficiency (MCM deficiency) is a type of methylmalonic acidemia caused by having too little methylmalonyl-CoA mutase. Methylmalonyl-CoA mutase (MCM) is one of the special proteins (enzymes) needed to breakdown certain amino acids found in the food we eat.
Where is Methylmalonyl-CoA Mutase found?
Methylmalonyl-CoA mutase is expressed in high concentrations in the kidney, in intermediate concentrations in the heart, ovaries, brain, muscle, and liver, and in low concentrations in the spleen. The enzyme can be found all throughout the central nervous system (CNS).
Where does Methylmalonyl-CoA come from?
The methylmalonyl-CoA unit that is the precursor to methyl-branched fatty acids and hydrocarbons arises from the carbon skeletons of valine and isoleucine, but not succinate (Dillwith et al., 1982).
Where does methylmalonyl-CoA come from?
What is MMA diagnosis?
An MMA test is most often used to diagnose a vitamin B12 deficiency. This test is also used to diagnose methylmalonic acidemia, a rare genetic disorder. Symptoms of this disorder can range from mild to severe and may include vomiting, dehydration, developmental delays, and intellectual disability.
How methylmalonyl-CoA is formed?
Acetyl-CoA enters directly into the TCA cycle. Propionyl-CoA undergoes carboxylation, producing the isomer D methylmalonyl-CoA via propionyl-CoA carboxylase, on which epimerase then converts to its L form and is subsequently isomerized to succinyl-CoA via MCM (Lehninger et al., 1993).
What is normal MMA level?
Methylmalonic acid (MMA) levels are commonly used to evaluate for vitamin B-12 deficiency. The normal value for MMA is < 3.6 μmol/mmol creatinine.
Where is Methylmalonyl CoA Mutase found?
What happens if MMA is high?
High MMA levels can be a sign of a vitamin B12 deficiency. Vitamin B12 deficiency can lead to serious health problems including anemia, a condition in which your blood has a lower than normal amount of red blood cells.
How are folic acid B12 and homocysteine related?
Homocysteine is an amino acid. Vitamins B12, B6 and folate break down homocysteine to create other chemicals your body needs. High homocysteine levels may mean you have a vitamin deficiency. Without treatment, elevated homocysteine increases your risks for dementia, heart disease and stroke.
Why is methylmalonic acid high in B12?
Vitamin B-12 is required for methylmalonic acid (MMA) to be converted to succinyl-CoA, and in combination with folic acid, for homocysteine (HC) to be converted to methionine [9]. Therefore, MMA is clearly more specific to vitamin B-12 deficiency compared to HC.
What is methylmalonyl-CoA mutase (MCM)?
Among them, methylmalonyl-CoA mutase (MCM) has been extensively studied. This enzyme catalyzes the reversible isomerization of L-methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin (AdoCbl) as a cofactor participating in the generation of radicals that allow isomerization of the substrate.
What is the role of vitamin B12 in methylmalonyl-CoA mutase?
Vitamin B(12) is an organometallic compound with important metabolic derivatives that act as cofactors of certain enzymes, which have been grouped into three subfamilies depending on their cofactors. Among them, methylmalonyl-CoA mutase (MCM) has been extensively studied.
What enzyme catalyzes the isomerization of methylmalonyl-CoA to succinyl CoA?
This vitamin B 12 -dependent enzyme catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA in humans. Mutations in MUT gene may lead to various types of methylmalonic aciduria.
How does coenzyme B12 convert methylmalonyl-CoA to 5-deoxyadenosine?
The 5′-deoxyadenosyl radical from coenzyme B 12 could abstract a hydrogen atom from the methyl group of methylmalonyl-CoA to form 5′-deoxyadenosine and the methylene radical of the substrate.