PA is a rare, life-threatening, inherited metabolic disorder due to a defect in the mitochondrial enzyme propionyl-CoA carboxylase
, or PCC.
Metabolic investigations revealed a diagnosis of propionic aciduria (PA) due to a deficiency in the enzyme propionyl-CoA carboxylase
Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase
, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects.
Patients are deficient in propionyl-CoA carboxylase
(PCC), an enzyme that utilizes certain amino acids found in protein.
EMA may be formed via carboxylation of accumulated butyryl-CoA, catalyzed by propionyl-CoA carboxylase
. The presence of methylsuccinic acid was also noted, likely produced from ethylmalonyl-CoA.
This patient has propionic acidemia (PA), caused by deficiency of propionyl-CoA carboxylase
(PCC) [EC number 126.96.36.199], a biotin-dependent, homododecameric enzyme involved in the catabolic pathways of isoleucine, valine, threonine, cholesterol, and odd-chain fatty acids.
This results in the accumulation of butyryl-CoA, which is converted to ethylmalonyl-CoA (by propionyl-CoA carboxylase
) and hydrolyzed to ethylmalonic acid.
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.sub.12] deficiency (n = 8) were identified prospectively during routine screening or made available by various screening laboratories with informed consent or submitted for routine second-tier testing.
Normally propionyl-CoA is metabolized to methylmalonyl-CoA by the action of propionyl-CoA carboxylase
(PCC), but if the metabolite is in excess the propionyl species is released from the mitochondrion after conversion by carnitine palmitoyl transferase II to the corresponding acylcarnitine (Fig.
PA results from a deficiency of mitochondrial propionyl-CoA carboxylase
, an enzyme that requires biotin as a cofactor and converts propionyl-CoA to D-methylmalonyl-CoA.
deficiency with overflow of metabolites of isoleucine catabolism at all levels.