Hexokinase properties

Brain hexokinase is inhibited by its product glucose-6-phosphate and to a lesser extent by adenosine diphosphate. The isoenzyme of hexokinase found in brain may be soluble in the cytosol or be attached firmly to mitochondria [2 and references therein]. An equilibrium exists between the soluble and the bound enzyme. The binding changes the kinetic properties of hexokinase and its inhibition by Glc-6-P resulting in a more active enzyme. The extent of binding is inversely related to the ATP ADP ratio, i.e. conditions in which energy utilization... 

NMR properties, 33 213, 274 partitioning, yeast hexokinase, 28 343, 344 tracer measurements, 32 320... 

Even within a single organism, the same enzyme, as defined by the reaction it catalyses, can exist in more than one form, each of which is the prodnct of a different gene. These are known as isoenzymes. The properties of the two enzymes are nsnally different and this may explain the different roles of the isoenzymes within either a single type of tissue or within different tissnes, e.g. glncokinase and hexokinase in the hepatocyte (see below). 

Symbol for the temperature coefficient, a quotient equal to Vt+wIvt, where Vr+io and Vj are the rates of a process (e.g., an enzyme-catalyzed reaction) at two temperatures differing by 10°C. This parameter is usually evaluated at saturating concentrations of substrate(s), so that temperature-dependent changes in Michaelis constant(s) are inconsequential. The <2io value is a characteristic property of a particular enzyme from a specific organism and cell type. For example, one cannot use the Qio value for one hexokinase from yeast to infer the temperature dependence of another hexokinase, say from rat brain. Likewise, the Qio value need not remain the same for a mutant form and a wild-type enzyme. 

Hexokinase is present in all cells of all organisms. Hepatocytes also contain a form of hexokinase called hexokinase IV or glucokinase, which differs from other forms of hexokinase in kinetic and regulatory properties (see Box 15-2). Two enzymes that catalyze the... 

A review of the four hexokinase isozymes of mammals their properties and tissue distributions and their expression during the development of tumors. 

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. 

FIGURE 15-16 Comparison of the kinetic properties of hexokinase IV (glucokinase) and hexokinase I. Note the sigmoidicity for hexokinase IV and the much lower Km for hexokinase I. When blood glucose rises above 5 itim, hexokinase IV activity increases, but hexokinase I is already operating near /max at 5 itim glucose and cannot respond to an increase in glucose concentration. Hexokinase I, II, and... 

This enzyme plays a key role in the metabolism of glucose and other related sugars. The physical and kinetic properties of yeast hexokinase have been extensively studied. Numerous recent studies have been made of its role in the phosphoryl transfer reaction. 

Hexokinase has a molecular weight of 102,000 and is composed of two identical subunits of 51,000 molecular weight each (20-22). In yeast, hexokinase exists as a mixture of two isoenzymes (23). These forms have been named A and B (23). These isoenzymes can be separated by chromatography and have been found to be chemically different (23, 24). Some of the earlier work with hexokinase was done with preparations that contained a mixture of isoenzymes. Work also was done with enzyme that was proteolytically modified. These variations undoubtedly have been responsible for some of the controversy concerning the properties of this enzyme. 

The standard free energy change is about —5 kcal/mol, and the equilibrium constant is about 5,700. Thus, equilibrium considerations indicate a potential for this reaction to occur. The potential can be converted to reality only by an enzyme with appropriate kinetic properties. Hexokinases purified from various tissues typically have a Michaelis constant for glucose between 10 and 20 /am. Thus, by the expenditure of ATP, hexokinase can convert glucose in the micromolar... 

J. G. Buchanan, D. M. Clode, and N. Vethaviyasar, Potential hexokinase inhibitors. Synthesis and properties of 2,3-anhydro-D-allose, 2,3-anhydro-D-ribose, and 2-0-methylsulphonyl-D-mannose, J. Chem. Soc., Perkin Trans. 1, (1976) 1449-1453. 

M. Szymona (1962). Purification and properties of the new hexokinase utilizing inorganic polyphosphate. Acta Biochim. Pol., 9,165-181. 

Although W-acetyl-D-glucosamine has inhibitory properties, it is apparently not phosphorylated. When AT-acetyl-D-glucosamine is added alone to ox-brain extracts, no carbon dioxide is produced. Yeast hexokinase... 

The reaction of 5 -amino-5 -deoxyadenosine with trimetaphosphate affords the 5 -Af-triphosphate (23). When (23) is employed as substrate with glucose in the hexokinase-catalysed reaction, the 5 -AT-diphosphate (24) is obtained the latter is cleaved by snake venom phosphodiesterase to the 5 -phosphoramidate, and hydrolyses in acid to the amino-nucleoside. It does not appear to be polymerized by polynucleotide phosphorylase. In this context it is noteworthy that uridine 5 -5-thiopyrophosphate (25) is a competitive inhibitor for polynucleotide phosphorylase from E. coli, but not a substrate, and that the 5 -S-thiotriphosphates (26) and (27) show neither substrate nor inhibitory properties for RNA polymerase or DNA polymerase I, respectively. However, (23) can be polymerized using the latter enzyme, showing that the introduction of a 5 -heteroatom does not completely exclude these modified nucleotides as substrates for the polymerizing enzymes. 

Kalab, P., Visconti, P., Leclerc, P., andKopf, G.S. (1994). p95, the major phosphotyrosine- containing protein in mouse spermatozoa, is a hexokinase with unique properties. J. Biol. Chem. 269 3810-3817. 

Table 4. Vesicant properties of a range of compounds compared with their capacity to inhibit the enzyme hexokinase in vitro (adapted from Dixon and Needham, 1946)...

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