Promoters hexokinase

Structural changes also contribute to the high specificity of some enzymatic reactions. In hexokinase, the structural change induced by glucose promotes the binding of the other substrate, ATP. ATP does not bind to the enzyme... 

M. M. Katabi, H. L. Chan, S. E. Karp, and G. Batist, Hexokinase type II a novel tumor-specific promoter for gene-targeted therapy differentially expressed and regulated in human cancer cells, Hum. Gene Ther. 70 155 (1999). 

Hexokinase is an enzyme that is mentioned at an early point in most biochemistry courses, since this enzyme is required for the first step in the body s utilization of glucose. The promoter for the hexokinase gene is shown here. This promoter consists of about 160 base pairs, and contains a TATA box (AATAA underlined), a CCAAT box [also underlined), and a short sequence of DNA that is regulated by a hormone. The hormone-regulated sequence is CCACGTCA (underlined). This short sequence of DNA is one of many types of "response elements" that occur in the genome. Specifically, CCACGTCA is called the cyclic AMP response element, for reasons that are explained later. This response element occurs in the hexokinase promoter, just a few nucleotides beyond the CCAAT box (Osawa rf a., 1996) ... 

Osawa, H., Robey, R, Frintz, R., and Gmnner, D. (1996). Identification and characicri7.ation of basal and cyclic AMP response elements in the promoter of the rat hexokinase II... 

Murakami K, Kanno H, Miwa S, PiomeUi S. Human HKr isozyme organization of the hexokinase I gene, the erythroid-specific promoter, and transcription initiation site. Mol Genet Metab 1999 67 118-30. 

A few inhibitors of these several enzymes are provided in Voet and Voet (1990). These include glucose-6-phosphate as an inhibitor for hexokinase, as it is a reaction product. Also, ATP and citrate are listed as inhibitors of PFK, and ATP is an inhibitor for pyruvate kinase, as it is a conversion product. Other inhibitors are tabulated in Appendix A of Hoffman s Cancer and the Search for Selective Biochemical Inhibitors (1999). On the other hand, Voet and Voet (1990) list a few activators or promoters for PFK, including ADP, fructose 6-phosphate (which is a reactant), fructose 1,6-bisphosphate (which is a product), the ammonium ion, and the orthophosphate ion Pj. The situation can get complicated. 

Therapeutics and target validation studies will certainly be tested in animals. Ribozymes have been used in transgenic mice to create disease models such as diabetes by selectively downregulating the hexokinase mRNA in pancreatic islets. In this case, the ribozyme expression was under the control of the insulin promoter, and was therefore only expressed in the pancreatic beta cells. Retroviral delivery of ribozymes targeted against neuregulin-1 in a chick blastoderm resulted in the same embryonic lethal... 

Hexokinase activity promotes the intracellular retention of glucose and thereby controls its rate of entry into carbohydrate metabolism whereas... 

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