This results in the accumulation of butyryl-CoA, which is converted to ethylmalonyl-CoA (by propionyl-CoA
carboxylase) and hydrolyzed to ethylmalonic acid.
Cobalamin deficiency results in the accumulation of precursor propionyl-CoA
, which in turn leads to odd-chain fatty acid synthesis, resulting in incorporation of large amounts of unusual C15 and C17 fatty acids in nerve sheets with altered nerve functions.
Malonyl-CoA reductase and propionyl-CoA
synthetase are the key enzymes of the 3-hydroxypropianate cycle, which is operative in Chloroflexus (Ishii et al.
organic acidurias such as glutaryl-CoA dehydrogenase, 3-hydroxy-3-methylglutaryl-CoA lyase, [beta]-ketothiolase, Propionyl-CoA
carboxylase, Methylmalonyl-CoA mutase, and Isovaleryl-CoA dehydrogenase) (Vreken et al.
Patients are deficient in propionyl-CoA
carboxylase (PCC), an enzyme that utilizes certain amino acids found in protein.
The monomeric composition of PHA polymers is determined by the substrate specificities of [beta]-ketothiolase and PHB synthase and by the availability of acetyl-CoA and propionyl-CoA
Since the propionyl-CoA
carboxylase enzyme reaction is reversible, propionyl-CoA
accumulates and conjugates to free carnitine to produce propionylcarnitine (Fig.
Samples obtained from the original NBS specimens of confirmed cases with [beta]-cystathionine synthase deficiency (n = 4), propionyl-CoA
carboxylase deficiency (n = 2), methylmalonyl-CoA mutase deficiency (n = 4), Cbl C deficiency (n = 7), various remethylation disorders [methylenetetrahydrofolate reductase (MTHFR), n = 3; Cbl G, n = 3; Cbl D variant 1, n = 1], and maternal vitamin [B.
is an intermediate in the degradation of several amino acids.
PA results from a deficiency of mitochondrial propionyl-CoA
carboxylase, an enzyme that requires biotin as a cofactor and converts propionyl-CoA
PA results from a defect in the enzyme propionyl-CoA
carboxylase, which catalyzes the biotin-dependent conversion of propionyl-CoA
to methylmalonyl-CoA (8).
carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels.