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Questions {❓}

• 1430-?
• Storgaard JH, Madsen KL, Lokken N, Vissing J, van Hall G, Lund AM, Orngreen MC (2020) Impaired lipolysis in propionic acidemia: a new metabolic myopathy?

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         headline:Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia
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      headline:Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia
      description:Propionic acidemia is an inborn error of metabolism caused by mutations in either the PCCA or PCCB genes. Patients with propionic acidemia experience a range of complications, including life-threatening cardiac dysfunctions. However, the pathological mechanisms underlying propionic acidemia-associated cardiac diseases remain largely unknown. To gain insights into the metabolic alterations in propionic acidemia, we studied human induced pluripotent stem cell-derived cardiomyocytes generated from a patient with propionic acidemia with two pathogenic PCCA mutations (p.Cys616_Val633del and p.Gly477Glufs9*) and from a healthy individual. Using stable isotope-based metabolic flux analysis, we confirmed that the PCCA mutations lead to impaired propionyl-CoA carboxylase activity in human induced pluripotent stem cell-derived cardiomyocytes. In addition to being converted to propionylcarnitine, the accumulated propionyl-CoA can also be hydrolyzed to propionate and exported out of the cell, serving as a secondary “pressure valve” to regulate cellular propionyl-CoA levels. Interestingly, the deficiency of propionyl-CoA carboxylase was found to shift fuel metabolism from fatty acid oxidation to increased glucose metabolism human in induced pluripotent stem cell-derived cardiomyocytes from patients with propionic acidemia. This metabolic switch is less energy-efficient and may contribute to the development of chronic cardiac dysfunction in patients with propionic acidemia.
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      dateModified:2025-04-02T00:00:00Z
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         Human induced pluripotent stem cell-derived cardiomyocytes
         Metabolic flux
         Glucose metabolism
         Fatty acid metabolism
         Cardiac diseases
         Cell Biology
         Biomedicine
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      name:Surgical Research Lab, Department of Surgery, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, USA
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