PA is a rare, life-threatening, inherited metabolic disorder due to a defect in the mitochondrial enzyme propionyl-CoA
carboxylase, or PCC.
This happens in some plants and marine organisms, because the last cycle of [beta]-oxidation provides propionyl-CoA
that can be converted to succinyl-CoA, which enters the cycle of citric acid.
Several enzymes are involved in the incorporation of these substrates in the gluconeogenesis pathway : lactate dehydrogenase (LDH) for lactate; glycerol kinase (GK) and glycerol-3-phosphate dehydrogenase (GPD) for glycerol; and acyl-CoA synthetase short-chain family member 3 (ACSS3), propionyl-CoA
carboxylase (PCC), methylmalonyl-CoA epimerase (MCEE), and methylmalonyl-CoA mutase (MUT) for propionate.
Metabolic investigations revealed a diagnosis of propionic aciduria (PA) due to a deficiency in the enzyme propionyl-CoA
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., 2004) with a modified version detected in the crenarchaeal order Sulfolobales (Alber et al., 2006).
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., 1999).
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
. In the case of 4- and 5-carbon PHA precursors, when [beta]-ketothiolase is encoded by phbA, a homopolymer of PHB is produced.
EMA may be formed via carboxylation of accumulated butyryl-CoA, catalyzed by propionyl-CoA
This patient has propionic acidemia (PA), caused by deficiency of propionyl-CoA
carboxylase (PCC) [EC number 188.8.131.52], 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.