Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction.
CRISPR-edited MUT and PCCA HEK293 cells recapitulate primary defects of MMA and PA and have upregulation of transcripts associated with serine and thiol metabolism including PSAT1.
We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients.
Our results suggest that at excess NH3, the DNA methylation status of the HIF-1α binding site of GPX3 in newborns with PA is demethylated (TGTTTTTTATG allele).
Deficiency of propionyl-CoA carboxylase causes propionic acidemia and deficiencies of methylmalonyl-CoA mutase or its cofactor adenosylcobalamin cause methylmalonic acidemia.
Our results suggest that at excess NH3, the DNA methylation status of the HIF-1α binding site of GPX3 in newborns with PA is demethylated (TGTTTTTTATG allele).
The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes.
The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes.
It can be assumed that acute and chronic effects of accumulating metabolites on the KvLQT1/KCNE1 channel protein may similarly cause the hearing impairment of patients with propionic acidemia.
Under these targeted conditions, both vectors mediated significant long-term correction of circulating metabolites, demonstrating that correction of muscle and likely other tissue types in addition to liver is necessary to fully correct pathology caused by PA. Liver-specific AAV8-TTR-PCCA mediated better correction than AAV1-MCK-PCCA.
The autosomal recessive disease propionic acidemia (PA) is an inborn error of metabolism with highly variable clinical manifestations, caused by a deficiency of propionyl-CoA carboxylase (PCC) enzyme, due to mutations in either PCCA or PCCB genes, which encode the alpha and beta subunits of the PCC enzyme, respectively.
Splicing defects account for 16% of the mutant alleles in the PCCA and PCCB genes, encoding both subunits of the propionyl-CoA carboxylase (PCC) enzyme, defective in propionic acidemia, one of the most frequent organic acidemias causing variable neurological impairment.
This initial screen has identified a range of mutant PCC proteins that are sufficiently stable to be purified and subsequently used for structure-function analysis to further elucidate the complex relationship between genotype and phenotype in propionic acidemia.
Thus, we have constructed three site-directed mutants of biotin carboxylase that are homologous to three missense mutations found in propionic acidemia or methylcrotonylglycinuria patients.
CRISPR-edited MUT and PCCA HEK293 cells recapitulate primary defects of MMA and PA and have upregulation of transcripts associated with serine and thiol metabolism including PSAT1.
<b>Background:</b> Propionic acidemia (PA) is an extremely rare autosomal recessive disorder which is caused by the deficiency of propionyl-CoA carboxylase (PCC) and associated with pathogenic variants in PCCA or PCCB gene.