The reactions that feed amino groups into the urea cycle

Excessaminoacidsinthebodycanbeusedasasourceofenergy,withtheircarbonskeletonconvertedtometabolicintermediatessuchasacetyl-CoAorintermediatesintheKrebscycle.Themetabolicbreakdownofaminoacidsreleasesnitrogenthatmustbeconvertedtoarelativelynon-toxicformandthenexcreted.Inmammals,thenitrogenisconvertedtoureaintheliverthroughaseriesofreactionscalledtheureacycle.Theammoniareleasedthroughthedeaminationofaminoacidsisreactedtoproducecarbamoylphosphate,areactioncatalyzedbycarbamoylphosphatesynthase.Theenzymeornithinetranscarbamoylaseisfoundinmitochondriaandconvertsornithineintocitrulline.Citrullineisexportedintothecytoplasmwhereanothernitrogenforureaisacquiredfromaspartate,followedbythereleaseoffumaratetoformtheaminoacidarginine.Ureaisreleasedfromargininebytheenzymearginase,bringingthecyclebackaroundtoornithine.Thegeneralrouteofentryforaminoacidsintotheureacycleisthroughtransamination,thetransferoftheiraminogrouptoalpha-ketoglutaratetoformglutamate.Theaminogroupfromglutamateisreleasedbyglutamatedehydrogenasetocreateanammoniumion.Theammoniumionisusedtomakecarbamoylphosphate,andultimatelyureathroughtheureacycle.Differentaminoacidscanenterthispathwaybydifferentroutes.Thetransferoftheaminogroupfromaspartatetoalpha-ketobutyratecreatesoxaloacetate,aKrebscycleintermediate.Alaninegoesthroughtransaminationtoreleasepyruvate,whichcanbeusedasfuel.Geneticdefectsthatcompletelyblocktheureacyclearenotobservedinpeople,perhapssincesuchadefectwouldbefatal.Mutationsthatreducetheactivityoftheureacyclehavebeenobserved,withseriousaffectsonmentalfunctioningandothertoxitiescausedbyelevatedlevelsofammonia.

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