Messenger RNA CodingforArgininosuccinate Synthetase inCitrullinemia

SUMMARY Messenger RNA coding forargininosuccinate synthetase (ASS), extracted fromthelivers ofsomepatients withcitrullinemia, wasanalyzed using acell-free translation system anddotandNorthern blot hybridization withcDNAprobeforASS. Inpatients withquantitative-type citrullinemia, called typeIIhere, previous studies havedemonstrated thatthehepatic content ofthe enzymewasabout10%ofthecontrol value, whereas thetranslatable mRNA level fortheenzymewassimilar tothat ofcontrol livers. Here, weconfirmed that thetypeIIliver contained analmost normal amount ofmRNA coding forASS,judged bythedot-blot hybridization technique withcDNA.Northern blot hybridization ofRNA indicated that there washybridizable mRNA ofapproximately normal size (about 1.7kilobase [kb]) ineach, suggesting thatlarge structural genedeletions hadnotoccurred. Theseresults indicate thatintypeIIcitrullinemia, thedecrease intheenzymeprotein isdueeither toincreased degradation oftheenzymeortodecreased orinhibited translation in theliver. Another typeofcitrullinemia wasfound andclassified astypeIII. It ischaracterized bynodetectable enzymeactivity forASSortranslationactivity forASSmRNA.However, asmaller amountofRNA molecule hybridized forASScDNAwasdetected.