Propionyl-CoA carboxylase – A review

Abstract

Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual presenting with metabolic acidosis, hyperammonemia, lethargy, vomiting and sometimes coma and death if not treated. Individuals with propionic acidemia also have a number of long term complications resulting from the dysfunction of the PCC enzyme. Here we present an overview of the current knowledge about the structure and function of PCC. We review an updated list of human variants which are published and provide an overview of the disease.

Pre‐school neurocognitive and functional outcomes after liver transplant in children with early onset urea cycle disorders, maple syrup urine disease, and propionic acidemia: An inception cohort matched‐comparison study

“…In PA, mitochondrial function is impaired leading to abnormal energy metabolism and increase susceptibility to neurological injury. 5 In MSUD, high leucine levels predispose to encephalopathy and neurological injury. Thus, pre-LT events may account for much of the differences between IEM and non-IEM patients both pre-and post-LT in neurological and functional outcomes.…”

“…4 Individuals with PA can also have significant intellectual disability and additionally show higher prevalence of autism spectrum disorder (ASD), optic nerve atrophy, and basal ganglia strokes. 5 Intellectual disability in MSUD is present, 6 although not as severe as in UCD and PA. In MSUD, attention deficit, hyperactivity, and mental health illnesses are prevalent.…”

“…In addition to intellectual disability and abnormal brain imaging, individuals with UCD are at risk of cerebral palsy, seizures, and cortical blindness . Individuals with PA can also have significant intellectual disability and additionally show higher prevalence of autism spectrum disorder (ASD), optic nerve atrophy, and basal ganglia strokes . Intellectual disability in MSUD is present, although not as severe as in UCD and PA.…”

Direct anabolic three carbon metabolism via propionate to a six carbon metabolite occurs in human heart and in vivo across mouse tissues

“…As described previously (17), 13 C-valine infusion was performed on 12-week old male C57/blk6 or db/db mice with a catheter surgically implanted on the right jugular vein. The mouse infusion setup included a tether and swivel system which permitted the mice to have free movement in the cage with bedding materials and free access to water.…”

“…Extreme pathological defects in propionate metabolism including propionic acidemia (PA), an inherited disorder caused by an aberrant function of propionyl-CoA carboxylase (PCC), result in significant morbidity and mortality (11) and systemic metabolic dysregulation (12). Although PA is often detectable by newborn screening, even after diagnosis, prognosis remains poor due to sub-clinical metabolic dysregulation, life-threatening metabolic decompensations, and sequelae from severe crisis (13). Especially during these metabolic crisis, patients with PA have high levels of organic acids and acylcarnitines in the blood and urine which include not only propionic acid/propionylcarnitine but also a wider dysregulated metabolome of mostly unidentified metabolites (14).…”