The authors studied the behavior of some enzymes involved in purine nucleotide metabolism in human peripheral blood lymphocytes from normal and B-cell chronic lymphocytic leukemia subjects. Determinations were made with radiochemical methods associated with high performance liquid chromatography. Results indicated a marked increase in de novo purine synthesis enzymes, particularly those of the « inosinic branch point ». The latter were absent in normal lymphocytes, whereas they were well evident in leukemic lymphocytes, with the exception of AMP-S synthetase. Whereas the enzymes of the « salvage pathway » were spared in comparison to other proteins, those of the « catabolic pathway » significantly decreased. The authors discuss the possibility that such enzymes may be used as tumor markers.
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References
1.
BarankiewiczJ., CohenA.: Purine nucleotide metabolism in phytohemagglutinin-induced human T lymphocytes.Arch. Biochem. Biophys., 258: 167–175, 1987.
2.
BontempsF., Van den BergheG., HersH.G.: Identification of a purine 5′-nucleotidase in human erythrocytes.Adv. Exp. Med. Biol., 195B: 283–290, 1986.
3.
BöyumA.: Isolation of leucocytes from human blood.Further observations. Scand. J. Clin. Lab. Invest., Suppl.97: 31–50, 1968.
4.
DaddonaP.E.: Human adenosine deaminase.Properties and turnover in cultured T and B lymphoblasts. J. Biol. Chem., 256: 12496–12501, 1981.
5.
De AbreuR.A., Van BaalJ.M., BakkerenJ.A.J.M., De BruynC.H.M.M.: High performance liquid chromatographic assay for identification and quantitation of nucleotides in lymphocytes and malignant lymphoblasts.J. Chromatogr., 227: 45–52, 1982.
6.
FairbanksL.D., GodayA., MorrisG.S., BrolsmaM.F., SimmondsH.A., GibsonT.: Rapid determination of purine enzyme activity in intact and lysed cells using high-performance liquid chromatography with and without radiolabelled substrates.J. Chromatogr., 276: 427–432, 1983.
7.
GreeneS.V., SmithJ.M.: High-performance liquid chromatographic detection of XMP as a basis for an improved IMP dehydrogenase assay.J. Chromatogr., 343: 160–167, 1985.
8.
HarmsenE., De JongJ.W., SerruysP.W.: Hypoxanthine production by ischemic heart demonstrated by high-pressure liquid chromatography of blood purine nucleosides and oxypurines.Clin. Chim. Acta, 115: 73–84, 1981.
9.
JacksonR.C., MorrisH.P., WeberG.: Increased adenylosuccinase activity in hepatomas and kidney tumors.Life Science, 18: 1043–1048, 1976.
10.
JacksonR.C., MorrisH.P., WeberG.: Partial purification, properties and regulation of inosine 5′-phosphate dehydrogenase in normal and malignant rat tissues.Biochem. J., 166: 1–10, 1977.
11.
LowryO.H., RosenbroughN.J., FarrA.L., RandallR.J.: Protein measurement with the Folin phenol reagent.J. Biol. Chem., 193: 265–275, 1951.
12.
MarijnenY.M.T., De KorteD., HaverkortW.A., Den BreejenE.J.S., Van GennipA.H., RossD.: Studies on the incorporation of precursors into purine and pyrimidine nucleotides via « de novo » and « salvage » pathways in normal lymphocytes and lymphoblastic cell-line cells.Biochim. Biophys. Acta, 1012: 148–155, 1989.
13.
MannelloE., Di StefanoA., PizzichiniM.: Purine metabolism in normal tissues and in tumors.Proceedings of II Italy-Republic of China Seminar, University of Sassari, March 29-30, 1983.
14.
PetersG.J., VeerkampJ.H.: Concentration, synthesis and utilization of phosphoribosylpyrophosphate in lymphocytes of five mammalian species.Int. J. Biochem., 10: 885–888, 1979.
15.
PetersG.J., OosterhofA., VeerkampJ.H.: Metabolism of purine nucleosides in human and ovine lymphocytes and rat thymocytes and their influence on mitogenic stimulation.Biochim. Biophys. Acta, 755: 127–136, 1983.
16.
PrajdaN., KatunumaN., MorrisH.P., WeberG.: Imbalance of purine metabolism in hepatomas of different growth rates, as expressed in behavior of glutamine phosphoribosyl-pyrophosphate amido transferase (amido-phosphoribosyl-transferase), (EC 2.4.2.14).Cancer Res., 35: 3061–3068, 1975.
17.
PrajdaN., MorrisH.P., WeberA.: Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC 1.2.3.2).Cancer Res., 36: 4639–4646, 1976.
RylanceH.J., WallaceR.C., NukiG.: Adenine phosphoribosyltransferase: assay using high performance liquid chromatography.Clinica Chimica Acta, 148: 267–272, 1985.
20.
ScholarE.M., CalabresiP.: Identification of the enzymatic pathways of nucleotide metabolism in human lymphocytes and leukemia cells.Cancer Res., 33: 94–103, 1975.
21.
SchultzV., LowensteinJ.M.: Purine nucleotide cycle: evidence for the occurrence of the cycle in brain.J. Biol. Chem., 251: 485–492, 1976.
22.
SimmondsH.A., GodayA., MorrisG., BrolsmaM.F.J.: Metabolism of deoxynucleoside by lymphocytes in long-term cultures deficient in different purine enzymes.Biochem. Pharmacol., 33: 763–770, 1984.
23.
SimmondsH.A., FairbanksL.D., DuleyJ.A., MorrisG.S.: ATP formation from deoxyadenosine in human erythrocytes: evidence for a hitherto unidentified route involving adenine and 5-S-adenosylhomocysteine hydrolase.Biosci. Rep., 9: 75–85, 1989.
24.
StanleyK.K., EdwardsM.R., LuzioJ.P.: Subcellular distribution and movement of 5′-nucleotidase in rat cells.Biochem. J., 186: 59–69, 1980.
Van LaarhovenJ.P.R.M., SpierenburgG. Th., De BruynC.H.M.M.: Enzymes of purine nucleotide metabolism in human lymphocytes.J. Immunol. Meth., 39: 47–58, 1980.
27.
Van LaarhovenJ.P.R.M., De GastG.C., SpierenburgG. Th., De BruynC.H.M.M.: Enzymological studies in chronic lymphocytic leukemia.Leukemia Res., 7: 261–267, 1983.
28.
Van LaarhovenJ.P.R.M., De BruynC.H.M.M.: Purine metabolism in relation to leukemia and lymphoid cell proliferation.Leukemia Res., 7: 451–480, 1983.
29.
VannoniD., PorcelliB., TabucchiA., LeonciniR., MannelloE.: Metabolismo dell'acido adenilosuccinico nel fegato di ratto.Communication to 34° Congr. Naz. SIB, Padova, 2-4 ottobre 1988.
30.
WattsR.W.E.: Purine enzymes and immune function.Clin. Biochem. Rev., 239–265, 1987.
31.
WeberG.: Enzymology of cancer cells (first of two parts).N. Engl. J. Med., 296: 486–493, 1977.
32.
WeberG.: Enzymology of cancer cells (second of two parts).N. Engl. J. Med., 296: 541–550, 1977.
33.
WeberG., LuiM.S., TakedaE., DentonJ.E.: Enzymology of human colon tumors.Life Sci., 27: 793–799, 1980.
34.
WelchM.M., RudolphF.B.: Regulation of purine biosynthesis and interconversion in the chick.J. Biol. Chem., 257: 13253–13256, 1982.
35.
WoodA.W., SeegmillerJ.A.: Properties of 5-phosphoribosyl-1 pyrophosphate amido-transferase from human lymphoblasts.J. Biol. Chem., 248: 138–143, 1973.
