Abstract
A purine nucleotide (inosinate) cycle is demonstrated with human lymphoblasts. The lymphoblast requires approximately 50 nmol of purine/10(6) cell increment. When the inosinate cycle is interrupted by the genetic, severe deficiency of either or both purine nucleoside phosphorylase (PNP) or hypoxanthine phosphoribosyltransferase (HPRT), purine accumulates in the culture medium as inosine, guanosine, deoxyinosine, and deoxyguanosine (PNP deficiency or PNP, HPRT deficiency) or hypoxanthine and guanine (HPRT deficiency). This accumulation represents an additional 25 to 32 nmol of purine which must be synthesized per 10(6) cell increment. PNP-deficient lymphoblasts have PPRibP contents characteristic of normal lymphoblasts, about 20 to 25 pmol/10(6) cells. HPRT-deficient lymphoblasts have four times higher PPRibP contents. The lymphoblast deficient for both PNP and HPRT has only a marginal elevation of PPRibP content, 1.5 times normal values. The elevated PPRibP content of HPRT-deficient cells reflects the efficient, unilateral reutilization of the ribose moiety of purine ribonucleotides and is not a cause of purine overproduction. Purine overproduction characterizing PNP-deficient lymphoblasts appears similar to overproduction from deficiency of HPRT, i.e. a break in the inosinate cycle rather than overactive de novo purine synthesis.
Highlights
A purine nucleotidecle is demonstrated fied in the serum and urine of patients with PNP deficiency with human lymphoblasts
We demonstrated the presence and magnitude relative to de m u o purine synthesis of a purine nucleotide cyclewhich utilized these same enzymes.We use the term inosinate cycle since IMP is the principle substrate in growing cultures, the ribose and purine moieties of AMP, GMP, and their corresponding deoxyribonucleosides are reutilized by the cycle [19, 20]
We show that the 4-fold elevated PPRibP content characterizing HPRT-deficient lymphoblasts may reflect the unilateral reutilization of the ribose moiety generated as shown in Fig. 1 from IMP
Summary
A purine nucleotide (inosinatcey)cle is demonstrated fied in the serum and urine of patients with PNP deficiency with human lymphoblasts. The lymphoblast requires as anaccumulation of the PNP substrates inosine, guanosine, approximately 60 nmol of purine/106 cell increment. Deoxyinosine, and deoxyguanosine [5, 9] and with HPRT. When the inosinatecycle is interrupted by the genetic, deficiency 4s an accumulation of uric acid(6-81, the principle severe deficiency of either or both purine nucleoside end product of catabolism of the HPRTsubstrates hypoxanphosphorylase(PNP)or hypoxanthine phosphoribosyl- thine and guanine. While the specific clinical manifestations Pomccbtt1or0iixlPee‘aea’ynn3dRnsgt2ciccsiuuseyybf,maenl))Plarn.mcTboaiaoonrsooshsneculiinritshotnee(eyf2nHomapp(0stcPPsoieuccntnxRNurhoeatimTaP,n.2nrgPe)u6tad,uhNwlceapaiptPnfhtnmeuiiei-coorcardoiinsheinselinn/tndfm1iericgec0cey,uui6paedasccorntenecerootbuilsnflxleenPmsynyeo.NsmituryHnsPmpnloaP,htaas(thRHoienHlneybsTPsPemlai-a,RRizddnpsaeTTedthdnsftiodithdpdhc-ioieeeeade2rnffvenii6cae---tul ltttwPhmhouihfauoPereevmnteRcrhfeaehaeoiteebanfselxnePsoltai,yhnesmmmneeaoiznon,pfoydraehvmpdomebutebrhtrorphleeidarrnoeaeoseepktfdeoeiluffciirsfnnciatyeehtetcntiniseohtotcs.hneniseeoouosisffnmibfsPopstashtNuyarierannPibtadnieentaeseonreoersxdcfeliycanstHrchtuaeeleltPetdtei.sRdotcIenfonTyrf,ocittcldtmhehhieeieefsinaanictcslciceetceouunvunmdlzemctyylumysumrwooeloaendnef-, lymphoblasts have four times higher PPRibP contents. The lymphoblast deficient for bPoNthP and HPRThas. Only a marginaellevationof PPRibP content1,.6 times normalvalues.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
