Editing Propionic acidemia (section)

==Pathophysiology==
[[File:Odd-chain FA oxydation.png|thumb|right|Propionic acidemia is caused by a defect in enzyme called propionyl-CoA carboxylase.]]
[[Image:autorecessive.svg|thumb|left|Propionic acidemia has an autosomal recessive pattern of [[inheritance]].]]
In healthy individuals, enzyme propionyl-CoA carboxylase converts [[propionyl-CoA]] to [[methylmalonyl-CoA]]. This is one of many steps in the process of converting certain [[amino acids]] and fats into energy. Individuals with propionic acidemia cannot perform this conversion because the enzyme propionyl-CoA carboxylase is nonfunctional. The essential amino acids [[valine]], [[methionine]], [[isoleucine]], and [[threonine]] can not be converted and this leads to a buildup of propionyl-CoA. Instead of being converted to methylmalonyl-CoA, propionyl-CoA is then converted into [[propionic acid]], which builds up in the bloodstream. This in turn causes an accumulation of dangerous acids and toxins, which can cause damage to the organs.{{Citation needed|date=June 2020}}

In many cases, propionic acidemia can damage the brain, heart, kidney, liver, cause seizures and delays to normal development such as walking or talking. The accumulation of propionic acid is known to induce differential responses in different organs. The heart and liver are specific targets of the complication.  The patient may need to be hospitalized to prevent breakdown of proteins within the body. Dietary needs must be closely managed.{{citation needed|date=October 2021}}

Mutations in both copies of the ''[[Propionyl-CoA carboxylase|PCCA]]'' or ''[[PCCB]]'' [[gene]]s cause propionic acidemia.<ref name="pamr">[http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm] {{webarchive|url=https://web.archive.org/web/20080829225331/http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm |date=2008-08-29 }}<br />Barry Lab - Vector and Virus Engineering. ''Gene therapy for Propionic Acidemia''</ref> These genes contain instructions to form alpha- and beta-subunits of PCC, the [[enzyme]] called propionyl-CoA carboxylase.{{cn|date=October 2024}}

PCC is required for the normal breakdown of the essential amino acids valine, isoleucine, threonine, and methionine, as well as certain odd-chained fatty-acids. Mutations in the ''PCCA'' or ''PCCB'' genes disrupt the function of the enzyme, preventing these acids from being metabolized. As a result, [[propionyl-CoA]], propionic acid, [[ketones]], [[ammonia]], and other [[toxic]] compounds accumulate in the [[blood]], causing the signs and symptoms of propionic [[acidemia]]. [[Hyperammonemia]] develops due to the inhibitory effects of propionyl-CoA on [[N-Acetylglutamate synthase|N-acetylglutamate synthase]], indirectly resulting in slowing of the [[urea cycle]].<ref>{{Cite journal|last1=Dercksen|first1=M.|last2=IJlst|first2=L.|last3=Duran|first3=M.|last4=Mienie|first4=L. J.|last5=van Cruchten|first5=A.|last6=van der Westhuizen|first6=F. H.|last7=Wanders|first7=R. J. A.|date=December 2014|title=Inhibition of N-acetylglutamate synthase by various monocarboxylic and dicarboxylic short-chain coenzyme A esters and the production of alternative glutamate esters|journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease|volume=1842|issue=12 Pt A|pages=2510–2516|doi=10.1016/j.bbadis.2013.04.027|issn=0006-3002|pmid=23643712|doi-access=free}}</ref>