Perl Andras
Department of Medicine, State University of New York Upstate Medical University, College of Medicine, Syracuse, New York 13210, USA.
IUBMB Life. 2007 Jun;59(6):365-73. doi: 10.1080/15216540701387188.
The signaling networks that mediate cell growth, differentiation, and survival are dependent on complex metabolic and redox pathways. Metabolism of glucose through the pentose phosphate pathway (PPP) fulfills two unique functions: formation of ribose 5-phosphate for the synthesis of nucleotides, RNA, and DNA in support cell growth and formation of NADPH for biosynthetic reactions and neutralization of reactive oxygen intermediates (ROI). Balancing of NADPH and ROI levels by the PPP enzyme transaldolase (TAL) regulates the mitochondrial trans-membrane potential (Deltapsi(m)), a critical checkpoint of ATP synthesis and cell survival. While complete deficiency of glucose 6-phosphate dehydrogenase (G6PD) or transketolase (TK) is lethal, TAL-deficient mice developed normally with the exception of male sterility due to structural and functional damage of sperm cell mitochondria. Recently, two cases of complete TAL deficiency have been reported in patients with liver cirrhosis which results from increased cell death of hepatocytes. Delineation of the cell type-specific role that TAL plays in the PPP and cell death signal processing will be critical for understanding the pathogenesis of TAL deficiency.
介导细胞生长、分化和存活的信号网络依赖于复杂的代谢和氧化还原途径。通过磷酸戊糖途径（PPP）进行的葡萄糖代谢具有两个独特功能：生成5-磷酸核糖用于合成核苷酸、RNA和DNA以支持细胞生长，以及生成NADPH用于生物合成反应和中和活性氧中间体（ROI）。PPP酶转醛醇酶（TAL）对NADPH和ROI水平的平衡调节线粒体跨膜电位（Δψm），这是ATP合成和细胞存活的关键检查点。虽然葡萄糖6-磷酸脱氢酶（G6PD）或转酮醇酶（TK）完全缺乏是致命的，但TAL缺陷小鼠除了因精子细胞线粒体的结构和功能损伤导致雄性不育外，发育正常。最近，在肝硬化患者中报告了两例完全TAL缺乏的病例，这是由肝细胞死亡增加所致。阐明TAL在PPP和细胞死亡信号处理中所起的细胞类型特异性作用对于理解TAL缺乏的发病机制至关重要。
