ADENOSINE TRANSPORT & METABOLISM

腺苷转运

• 批准号: 6308554
• 负责人: JAMES B BASSINGTHWAIGHTE
• 金额: $ 2.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6308554
• 关键词: Mammalia; bioengineering /biomedical engineering; biomedical resource; human tissue; model design /development; technology /technique

There is uncertainty about which metabolic pathway is most important for controlling myocardial cytosolic adenosine concentrations in the normoxic heart: AMP hydrolysis, linked to energetic status, or energy independent transmethylation (via S-adenosylhomocysteine hydrolysis) To answer this question, intracellular cycling of AMP and adenosine was abolished using an intracoronary infusion of the adenosine kinase blocker iodotubercidin (ITC), in the presence of adenosine deaminase inhibition. ITC caused a 10-fold increase in the coronary venous release rate of adenosine to 3.4 + 0.3 (mean + SE, n=5) nmol min-1g-1, representing total normoxic myocardial adenosine production. To determine the relative roles of AMP hydrolysis and transmethylation, parallel experiments tested the effect of ITC during blockade of transmethylation using adenosine dialdehyde. In these experiments, venous adenosine release increased to similar levels of 3.4 + 0.5 (n=6) nmol min-1g-1. The possibility that ITC caused increased adenosine release by interfering with myocardial energetics was ruled out in separate 31P NMR experiments. Mathematical modeling analysis of the adenosine results indicated that AMP-adenosine cycling causes increased sensitivity of cytosolic adenosine concentrations to increases in the rate of AMP hydrolysis. It is concluded that 1) at least 90% of the adenosine produced intracellularly is normally rephosphorylated to AMP without escaping into the venous effluent, 2) AMP hydrolysis is the dominant pathway for normoxic adenosine production, and 3) AMP-adenosine cycling serves to amplify the relative importance of energy dependent AMP hydrolysis over that of transmethylation in controlling cytosolic adenosine concentrations.

目前还不确定哪种代谢途径最重要， 对于控制心肌胞浆腺苷 含氧量正常的心脏中的浓度：AMP水解，与 能量状态，或能量非依赖性转甲基化（通过 S-腺苷高半胱氨酸水解）为了回答这个问题， AMP和腺苷的细胞内循环被消除， 冠状动脉内输注腺苷激酶阻断剂碘杀结核菌素 (ITC)在腺苷脱氨酶抑制剂存在下。 ITC造成 腺苷的冠状静脉释放速率增加10倍， 3.4+ 0.3（平均值+ SE，n=5）nmol min-1g-1，代表总含氧量正常 心肌腺苷生成。 确定的相对作用 AMP水解和甲基转移，平行实验测试了 ITC在腺苷阻断转甲基作用中作用 二醛 在这些实验中，静脉腺苷释放增加 至相似水平3.4 ± 0.5（n=6）nmol min-1 g-1。 的可能性 ITC通过干扰腺苷的释放， 在单独的31 P NMR实验中排除了心肌能量学。 腺苷结果的数学建模分析表明， AMP-腺苷循环导致细胞质对腺苷的敏感性增加。 腺苷浓度增加AMP水解速率。 结论是：1）至少90%的腺苷产生 细胞内的磷酸化酶通常再磷酸化为AMP而不逃逸 2）AMP水解是主要途径 用于含氧量正常的腺苷产生，和3）AMP-腺苷循环用于 为了放大能量依赖性AMP水解的相对重要性， 在控制胞浆腺苷方面， 浓度的