biostudies-literatureRichard ENational Center for Advancing Translational SciencesNCATS NIH HHSNational Institute on Alcohol Abuse and AlcoholismFundación Ramón ArecesPropionic Acidemia FoundationNIAAA NIH HHSUniversidad Autónoma de Madrid137https://www.ebi.ac.uk/biostudies/studies/S-EPMC11965053biostudies-literatureUnknown82(1)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 pCellular and molecular life sciences : CMLSMetabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia.PMC11965053R01 AA030026R21TR005163R21 TR005163PAF113XX National Call 2020NIH R01 AA030026Alvarez MHe WZhang GFRichard EChen XMarchuk HDesviat LRfalseMetabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia.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 p2025-01-01T00:00:00Z2025 Apr2026-05-28T03:15:45.086Z2026-05-28T03:06:26.909ZS-EPMC119650534017267310.1007/s00018-025-05661-5