Hexokinase mammalian

Coe and Bessell and coworkers studied the metabolic fates of 2-deoxy-2-fluoro-D-glucose (2DFG) and related compounds by using yeast hexokinase (as a model for mammalian hexokinase), and determined the kinetic constants K and V ) of the Michaelis-Menten equation D-glucose 0.17 (K in mAf)> 1 00 (relative value, D-glucose taken as 1) 2DG 0.59 0.11, 0.85 2DFG 0.19 0.03, 0.50 2-deoxy-2-fluoro-D-mannose (2DFM) 0.41 0.05, 0.85 2-deoxy-2,2-difluoro-D-nraZ>//Jo-hexose... 

Haldane relationships can also be useful in characterizing isozymes or the same enzyme isolated from a different source. Reactions catalyzed by isozymes must have identical equilibrium constants, but the magnitudes of their kinetic parameters are usually different (e.g., the case of yeast and mammalian brain hexokinase ). Note that the Haldane relationship for the ordered Bi Bi mechanism is = Hmax,f p i iq/(f max.r ia b)- This same... 

The substrate specificities of both mammalian and yeast hexo-kinases have been extensively studied (76,77). Nevertheless, work in this area continues both in the search for isoenzyme specific inhibitors and in increasingly detailed investigations of the catalytic mechanism. Recently potential transition state analogs PI-(adenosine-5 )-P3-glucose-6 triphosphate (Ap -glucose) and P1-(adenosine-5 )-P4-glucose-6 triphosphate (Ap.-giucose) were tested as inhibitors of four hexokinase isoenzymes. However, they were found to exhibit less affinity for the enzyme than either of the natural substrates alone (78). 

Smith, T.A. (2000) Mammalian hexokinases and their abnormal expression in cancer. Br. J. Biomed. Sci. 57, 170-178. 

The four forms of hexokinase found in mammalian tissues are but one example of a common biological situation the same reaction catalyzed by two or more different molecular forms of an enzyme. These multiple forms, called isozymes or isoenzymes, may occur in the same species, in the same tissue, or even in the same cell. The different forms of the enzyme generally differ in kinetic or regulatory properties, in the cofactor they use (NADH or NADPH for dehydrogenase isozymes, for example), or in their subcellular distribution (soluble or membrane-bound). Isozymes may have similar, but not identical, amino acid sequences, and in many cases they clearly share a common evolutionary origin. 

Mulichak AM, Wilson JE, Padmanabhan K, Garavito RM. The structure of mammalian hexokinase-1. Nat Struct Biol 1998 5 555-60. 

Wilson, J. E. 2003. Isozymes of mammalian hexokinase Structure, function and subcellular location. J. Exp. Biol. 206 2049-2057. Lee. Y. H., Li, Y., Uyeda. K., and Hasemann. C. A. 2003. Lissue-spe-cific structure/funclion differentiation of the five isoforms of 6-phosphofructo-2 kinase/lruclose-2,6 bisphosphatase. 7-... 

Glucose metabolism is controlled differently In various mammalian tissues to meet the metabolic needs of the organism as a whole. During periods of carbohydrate starvation, for instance, glycogen In the liver Is converted directly to glucose 6-phosphate (without Involvement of hexokinase). Under these conditions, there Is a reduction in fructose 2,6-bisphos-... 

Mammalian hexokinase exists in four major isoen-zymic forms that can be separated by electrophoresis. The distribution pattern is the same in different tissues of rat, hamster, rabbit, monkey, and cow for types I, II, and III. Type IV has been found only in liver [33]. 

Grossbard, L., Weksler, M., Schimke, R.T. Electrophoretic properties and tissue distribution of multiple forms of hexokinase in various mammalian species. Biochem. biophys. Res. Commun. 24, 32-38 (1966)... 

A possible direct effect of insulin on the hexoklnase reaction has been the subject of much speculation. Conflicting reports on the matter have done little to provide conclusive evidence in support of such a role for insulin. The nature and function of the various mammalian hexokinases have been reviewed.39 Rat liver hexoklnase exists in 4 electrophoretlcalJy distinguishable forms and one of these, hexoklnase II, can be further fractionated into 2 different forms.39 one form of hexoklnase II Is diminished In diabetic animals and levels of this enzyme are restored to normal by insulin.39... 

Despite these reservations, use of either the relative maximal capacity or the equilibrium/nonequilibrium reaction approach identifies the same enzymes as catalyzing potentially rate-controlling reactions. For example, in most mammalian tissues both methods suggest that the potential exists for control of glycolytic flux at the hexokinase, phosphofructokinase, and pyruvate kinase reactions (cf. Newsholme and Start, 1973). 

---