EFFECTS OF ADENOSINE-ANALOGS ON ATP CONCENTRATIONS IN HUMAN ERYTHROCYTES - FURTHER EVIDENCE FOR A ROUTE INDEPENDENT OF ADENOSINE KINASE
EFFECTS OF ADENOSINE-ANALOGS ON ATP CONCENTRATIONS IN HUMAN ERYTHROCYTES - FURTHER EVIDENCE FOR A ROUTE INDEPENDENT OF ADENOSINE KINASE
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DOI：
10.1016/0006-2952(91)90514-6
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发表时间：
1991-10-09
影响因子：
5.8
通讯作者：
SIMMONDS, HA
中科院分区：
文献类型：
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作者：
SMOLENSKI, RT;MONTERO, C;SIMMONDS, HA
腺苷衍生物因其强大的抗肿瘤、抗病毒和抗寄生虫活性而经常用于化疗。我们研究了一些腺苷类似物在腺苷脱氨酶抑制的正常和腺嘌呤磷酸核糖转移酶(APRT)缺陷的人红细胞中的代谢。测定细胞内ATP和GTP浓度及异常核苷酸的形成。所研究的一些类似物(结节杀菌素、9-β-D-阿拉伯呋喃核糖腺苷、2‘-脱氧腺苷、2-氯腺苷、奈普罗星A)被磷酸化成相应的核苷三磷酸盐，这一过程可被腺苷酶抑制剂碘结节苷所阻断。除2‘-脱氧腺苷外，核苷酸类似物的形成都伴随着ATP的耗竭。2‘-脱氧腺苷、新普兰素A和5’-碘-5‘-脱氧腺苷共同作用时，ATP浓度甚至升高。然而，在APRT缺乏的红细胞中没有观察到后者的增加。灯盏花素、S-腺苷同型半胱氨酸、脱氧康福霉素和腺苷二醛不形成核苷酸衍生物，也不对三磷酸腺苷浓度产生任何影响。结果表明，腺苷类似物既可以通过磷酸化机制进入核苷酸池，也可以通过腺嘌呤的中间形成途径转化为ATP。
Adenosine derivatives are frequently used in chemotherapy because of their potent antitumor, antiviral and antiparasitic activity. We investigated the metabolism of some adenosine analogues in adenosine deaminase inhibited normal and adenine phosphoribosyltransferase (APRT) deficient human erythrocytes. The ATP and GTP concentrations and the formation of unusual nucleotides were measured. Some of the analogues studied (tubercidin, 9-beta-D-arabinofuranosyladenine, 2'-deoxyadenosine, 2-chloroadenosine, neplanocin A) were phosphorylated to the corresponding nucleoside triphosphates and this process was abolished by iodotubercidin - an adenosine kinase inhibitor. With the exception of 2'-deoxyadenosine, nucleotide analogue formation was accompanied by ATP depletion. ATP decrease was not observed after adenosine kinase inhibition and ATP concentration even increased in the presence of 2'-deoxyadenosine, neplanocin A and 5'-iodo-5'-deoxyadenosine. However, the latter increment was not observed in APRT deficient erythrocytes. Bredinin, S-adenosylhomocysteine, deoxycoformycin and adenosine dialdehyde did not form nucleotide derivatives or exert any effects on ATP concentration. It is concluded that adenosine analogues can either enter the nucleotide pool via phosphorylation mechanisms, or may be converted to ATP by the pathways involving the intermediate formation of adenine.