ArticleJournal of inherited metabolic disease2023
Relief of CoA sequestration and restoration of mitochondrial function in a mouse model of propionic acidemia.
Article in Journal of inherited metabolic disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Article
- Energetic stress in combination with impaired fatty acid oxidation induces sequestration of CoA and adaptation of CoA metabolism.The FEBS journal · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Sulfonamide Pantothenate Kinase Activators and Elucidation of the Role of Isoform Selectivity in Cellular Pantothenate Kinase Activation.Journal of medicinal chemistry · 2026Article
- Emergency Management of Intoxication-Type Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2025Review
- Elevated propionate and its association with neurological dysfunctions in propionic acidemia.Frontiers in molecular neuroscience · 2025Review
- The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.Basic research in cardiology · 2024Article
- Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators.Journal of medicinal chemistry · 2024Article
- Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation.Communications biology · 2024Article
- Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.Molecular therapy. Methods & clinical development · 2023Article
- Starving the Beast: Limiting Coenzyme A Biosynthesis to Prevent Disease and Transmission in Malaria.International journal of molecular sciences · 2023Review
- Prevalence of propionic acidemia in China.Orphanet journal of rare diseases · 2023Review
- Pathophysiological mechanisms of complications associated with propionic acidemia.Pharmacology & therapeutics · 2023Review
- Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments.International journal of molecular sciences · 2023Review
- Relief of CoA sequestration and restoration of mitochondrial function in a mouse model of propionic acidemia.Journal of inherited metabolic disease · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Propionic acidemia (PA, OMIM 606054) is a devastating inborn error of metabolism arising from mutations that reduce the activity of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). The defects in PCC reduce the concentrations of nonesterified coenzyme A (CoASH), thus compromising mitochondrial function and disrupting intermediary metabolism. Here, we use a hypomorphic PA mouse model to test the effectiveness of BBP-671 in correcting the metabolic imbalances in PA. BBP-671 is a high-affinity allosteric pantothenate kinase activator that counteracts feedback inhibition of the enzyme to increase the intracellular concentration of CoA. Liver CoASH and acetyl-CoA are depressed in PA mice and BBP-671 treatment normalizes the cellular concentrations of these two key cofactors. Hepatic propionyl-CoA is also reduced by BBP-671 leading to an improved intracellular C3:C2-CoA ratio. Elevated plasma C3:C2-carnitine ratio and methylcitrate, hallmark biomarkers of PA, are significantly reduced by BBP-671. The large elevations of malate and α-ketoglutarate in the urine of PA mice are biomarkers for compromised tricarboxylic acid cycle activity and BBP-671 therapy reduces the amounts of both metabolites. Furthermore, the low survival of PA mice is restored to normal by BBP-671. These data show that BBP-671 relieves CoA sequestration, improves mitochondrial function, reduces plasma PA biomarkers, and extends the lifespan of PA mice, providing the preclinical foundation for the therapeutic potential of BBP-671.
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