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实验性糖尿病大鼠肾上腺中磷酸核糖焦磷酸的形成与肾上腺生长的关系

Phosphoribosyl pyrophosphate formation in the rat adrenal gland in relation to adrenal growth in experimental diabetes.

作者信息

Kunjara S, Sochor M, Ahmed S, Greenbaum A L, McLean P

机构信息

Department of Biochemistry, University College and Middlesex School of Medicine, London, UK.

出版信息

Diabetes. 1992 Nov;41(11):1429-35. doi: 10.2337/diab.41.11.1429.

Abstract

Adrenal growth occurs in experimental diabetes, and evidence exists for increased adrenal function. The concentration of PPRibP has been examined in the rat adrenal gland at various times after induction of diabetes with STZ, in view of the key role it plays in the synthesis of Purs and Pyrs. The PPRibP level was exceptionally high in the adrenal gland and increased faster than the rate of growth during the initial rapid growth phase--the first 7 days after STZ was given; PPRibP synthetase showed a parallel increase. Formation of R5P via the oxidative and nonoxidative segments of the PPP also was measured. The oxidative enzymes, G-6-PD and 6-PGD, increased in parallel with growth during the early phase, but showed a more marked rise during the secondary, slower, growth phase seen 6 wk after STZ was given, when this may be associated with the known sustained rise in plasma corticosteroids. The nonoxidative enzymes of the PPP, an alternate route for the production of R5P, showed smaller changes. The specifically high adrenal concentration of PPRibP may be related to the high Km for PPRibP (250 microM) of the first enzyme of the de novo pathway of Pur synthesis, as such synthesis may be required in the rat to replace the net loss of ATP associated with catecholamine secretion. Factors controlling PPRibP synthetase and their potential relative importance in the adrenal gland have been considered.

摘要

在实验性糖尿病中肾上腺会生长,且有证据表明肾上腺功能增强。鉴于PPRibP在嘌呤和嘧啶合成中起关键作用,已在链脲佐菌素诱导糖尿病后的不同时间点检测了大鼠肾上腺中PPRibP的浓度。在肾上腺中,PPRibP水平异常高,并且在最初的快速生长阶段(给予链脲佐菌素后的前7天)比生长速率增加得更快;PPRibP合成酶也呈现平行增加。还测量了通过磷酸戊糖途径的氧化和非氧化部分形成5-磷酸核糖(R5P)的情况。氧化酶葡萄糖-6-磷酸脱氢酶(G-6-PD)和6-磷酸葡萄糖酸脱氢酶(6-PGD)在早期与生长平行增加,但在给予链脲佐菌素6周后出现的次级、较慢生长阶段显示出更明显的上升,此时这可能与已知的血浆皮质类固醇持续升高有关。磷酸戊糖途径的非氧化酶作为产生R5P的另一条途径,变化较小。肾上腺中PPRibP的特异性高浓度可能与嘌呤合成从头途径中第一种酶对PPRibP的高Km值(250微摩尔)有关,因为在大鼠中可能需要这种合成来弥补与儿茶酚胺分泌相关的ATP净损失。已经考虑了控制PPRibP合成酶的因素及其在肾上腺中的潜在相对重要性。

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