Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum

Vincent A. Funari , Victoria L.M. Herrera , Daniel Freeman , Dean R. Tolan
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引用次数: 47

Abstract

Since 1967, fructose has become the primary commercial sweetener in the food industry. Large amounts of fructose can be toxic and have been correlated with atherosclerosis, malabsorption, hyperuricemia, lactic acidosis, and cataracts. To understand the deleterious and critical role(s) fructose plays in normal metabolism, it is essential to know how and where fructose is metabolized. The fructose transporter, GLUT5, and the specialized enzymes ketohexokinase, aldolase, and triokinase comprise the well-defined fructose-specific metabolic pathway found in liver, kidney, and small intestine. It is estimated that 50–70% of ingested fructose is metabolized in these tissues; where and how the remaining 30–50% is metabolized is not well defined. Prediction of tissues capable of metabolizing fructose via this pathway was done using expressed sequence tags (ESTs) in Unigene and a gene-specific virtual northern blot (VNB) algorithm. Unigene and VNB combined correctly predicted the expression of the genes required for fructose metabolism in liver, kidney, and small intestine. Both methods indicated brain, breast, lymphocytes, muscle, placenta, and stomach additionally express this set of genes. Expression of the genes for GLUT5 (glut5) and ketohexokinase (khk) in neurons was validated by immunohistochemistry and RNA in situ hybridization, respectively. Using stringent controls, clear expression of glut5 and khk was localized to Purkinje cells in the cerebellum. Cerebellum was used to oxidize fructose to carbon dioxide. Together, these data suggest that these neurons in the brain are able to utilize fructose as a carbon source.

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果糖代谢所需的基因在小脑浦肯野细胞中表达
自1967年以来,果糖已成为食品工业中主要的商业甜味剂。大量的果糖可能是有毒的,并且与动脉粥样硬化、吸收不良、高尿酸血症、乳酸酸中毒和白内障有关。要了解果糖在正常代谢中所起的有害和关键作用,就必须知道果糖是如何以及在哪里代谢的。果糖转运体GLUT5和专门的酶酮己糖激酶、醛缩酶和三磷酸激酶组成了肝脏、肾脏和小肠中明确的果糖特异性代谢途径。据估计,摄入的果糖中有50-70%在这些组织中代谢;剩余的30-50%在哪里以及如何被代谢还没有很好的定义。通过Unigene中的表达序列标签(est)和基因特异性虚拟北方印迹(VNB)算法,预测能够通过该途径代谢果糖的组织。Unigene和VNB结合正确预测了肝脏、肾脏和小肠中果糖代谢所需基因的表达。两种方法均表明,脑、乳腺、淋巴细胞、肌肉、胎盘和胃也表达这组基因。采用免疫组织化学和RNA原位杂交技术分别验证了神经元中GLUT5 (GLUT5)和酮己糖激酶(khk)基因的表达。通过严格的对照,glut5和khk的明确表达定位于小脑浦肯野细胞。用小脑将果糖氧化为二氧化碳。总之,这些数据表明,大脑中的这些神经元能够利用果糖作为碳源。
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Editorial Board Author Index Co-expression of the 5-HT3B subunit with the 5-HT3A receptor reduces alcohol sensitivity Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum Tolloid-like 1 is negatively regulated by stress and glucocorticoids
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