Article

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

Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Molecular Brain Research (Impact Factor: 2). 01/2006; 142(2):115-22. DOI: 10.1016/j.molbrainres.2005.09.019
Source: PubMed

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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    • "Until recently, GLUT5 was detected only in microglia in the central nervous system (CNS), its function unknown (Payne et al, 1997; Sasaki et al, 2004), but strengthening the case for the presence of fructose in the brain. Recently, the GLUT5 transporter has been shown in cerebellar Purkinje and granule cells in human fetus (Nualart et al, 1999) and Purkinje cells in mouse cerebellum (Funari et al, 2005). The function is not yet known but their presence does imply active fructose metabolism in this tissue. "
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