Flexibility in energy metabolism supports hypoxia tolerance in Drosophila flight muscle: metabolomic and computational systems analysis.
Flexibility in energy metabolism supports hypoxia tolerance in Drosophila flight muscle: metabolomic and computational systems analysis.
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DOI：
10.1038/msb4100139
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发表时间：
2007
影响因子：
9.9
通讯作者：
Paternostro, Giovanni
中科院分区：
文献类型：
--
作者：
Feala, Jacob D.;Coquin, Laurence;McCulloch, Andrew D.;Paternostro, Giovanni
果蝇（Drosophila melanogaster）是一种在细胞水平上研究低氧适应性的遗传学模型，但果蝇极端低氧耐受性的代谢基础尚不清楚。使用1H NMR光谱，在缺氧条件下收集代谢组学谱。乳酸、丙氨酸和乙酸的积累表明这些是果蝇厌氧代谢的主要终产物。一个基于约束的模型ATP生产途径的注释基因组，现有的模型，和文献。添加用于生产乙酸盐和丙氨酸的多个冗余途径，并进行模拟，以找到用于生产每种终产物的单一最佳策略。然后使用改进的模型在计算机上研究了对缺氧的全系统适应。模拟结果支持了这一假设，即丙酮酸灵活地转化为这三种副产物的能力可能通过提高ATP/H+比和葡萄糖利用效率来传递缺氧耐受性。
The fruitfly Drosophila melanogaster offers promise as a genetically tractable model for studying adaptation to hypoxia at the cellular level, but the metabolic basis for extreme hypoxia tolerance in flies is not well known. Using 1H NMR spectroscopy, metabolomic profiles were collected under hypoxia. Accumulation of lactate, alanine, and acetate suggested that these are the major end products of anaerobic metabolism in the fly. A constraint-based model of ATP-producing pathways was built using the annotated genome, existing models, and the literature. Multiple redundant pathways for producing acetate and alanine were added and simulations were run in order to find a single optimal strategy for producing each end product. System-wide adaptation to hypoxia was then investigated in silico using the refined model. Simulations supported the hypothesis that the ability to flexibly convert pyruvate to these three by-products might convey hypoxia tolerance by improving the ATP/H+ ratio and efficiency of glucose utilization.
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DOI：
10.1152/ajpendo.00464.2005
发表时间：
2006-04-01
影响因子：
5.1
作者：
Wadley, GD;Lee-Young, RS;McConell, GK
通讯作者：
McConell, GK
影响因子：
2.2
作者：
Krishnan, SN;Sun, YA;Haddad, GG
通讯作者：
Haddad, GG
影响因子：
4.8
作者：
Vo, TD;Greenberg, HJ;Palsson, BO
通讯作者：
Palsson, BO
影响因子：
7.4
作者：
Weljie, Aalim M.;Newton, Jack;Slupsky, Carolyn M.
通讯作者：
Slupsky, Carolyn M.
影响因子：
7
作者：
Reed, JL;Palsson, BO
通讯作者：
Palsson, BO