ArticleScience translational medicine2021
Pantothenate kinase activation relieves coenzyme A sequestration and improves mitochondrial function in mice with propionic acidemia.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Mechanistic pathways linking gut microbial metabolites, microbial structural products, and host-microbe co-metabolites to mitochondrial function.Gut microbes · 2026Pooled it
- 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
- Genetic and Multi-Omics Insights Into Monocyte Pantothenate-Mediated Protection in Acute Respiratory Distress Syndrome.Journal of cellular and molecular medicine · 2025Article
- 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
- Formal [4 + 2] combined ionic and radical approach of vinylogous enaminonitriles to access highly substituted sulfonyl pyridazines.Communications chemistry · 2024Article
- Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators.Journal of medicinal chemistry · 2024Article
- Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles.Metabolites · 2024Article
- Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation.Communications biology · 2024Article
- Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation.Nature cardiovascular research · 2023Article
- Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition.Nature chemical biology · 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
- Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- The pyridazine heterocycle in molecular recognition and drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Propionic acidemia (PA) is a rare autosomal-recessive metabolic disease that arises from mutations in propionyl-CoA (C3-CoA) carboxylase. Reduced enzyme activity slows C3-CoA metabolism, leading to an elevated plasma C3:C2-carnitine ratio, the hallmark biomarker of PA. The metabolic imbalances experienced in PA are however poorly defined. Here, we used a hypomorphic PA mouse model to demonstrate that C3-CoA accumulation in liver reduced non-esterified CoA (CoASH) and acetyl-CoA (C2-CoA). Tricarboxylic acid (TCA) cycle intermediates that are normally metabolized instead accumulated in urine, providing direct evidence for compromised mitochondrial function in PA. Pantothenate kinase (PanK) is known to catalyze the rate-controlling step in CoA biosynthesis, and its inhibition by C3-CoA prevents an increase in CoA biosynthesis to alleviate CoASH sequestration. PZ-3022 is an allosteric PanK activator that counteracts C3-CoA inhibition. PZ-3022 therapy increased hepatic CoASH and C2-CoA and decreased C3-CoA in the PA mouse model, leading to improved intracellular C3:C2-CoA and plasma C3:C2-carnitine ratios. Elevated urinary malate is a major component of the metabolic signature for TCA cycle dysfunction in the PA mouse, and the 80% reduction in urine malate by PZ-3022 therapy indicates the restoration of mitochondrial function. Thus, CoASH sequestration in PA leads to reduced TCA cycle activity that is relieved by PZ-3022, providing preclinical proof of concept for PanK activators as a therapy to attenuate the underlying mitochondrial defect in PA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.