Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum. 1626 70

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production.
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PMID:Specific regions of the brain are capable of fructose metabolism. 2803 22