Hexokinase glycolysis

See also Reactions/Energies of Glycolysis, Regulation of Glycolysis, Hexokinase... 

Another simple sugar that enters glycolysis at the same point as fructose is mannose, which occurs in many glycoproteins, glycolipids, and polysaccharides (Chapter 7). Mannose is also phosphorylated from ATP by hexokinase, and the mannose-6-phosphate thus produced is converted to fructose-6-phosphate by phosphomannoisomerase. 

Figure 5.3 Major control points of glycolysis and the TCA cycle. Enzymes I, hexokinase II, phosphofructokinase III, pyruvate kinase IV, pyruvate dehydrogenase V, citrate synthase VI, aconitase VII, isocitrate dehydrogenase VIII, a-oxoglutarate dehydrogenase.

It may be identified as a nonequilibrium reaction in which the of the enzyme is considerably lower than the normal substrate concentration. The first reaction in glycolysis, catalyzed by hexokinase (Figure 17-2), is such a flux-generating step because its for glucose of 0.05 mmol/L is well below the normal blood glucose concentration of 5 mmol/L. 

Glycolysis is regulated by three enzymes catalyzing nonequilibrium reactions hexokinase, phosphoffuc-tokinase, and pyruvate kinase. 

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

The role of L-glycerose as a precursor of l sugars is doubtful, since it inhibits glycolysis in plants and animals, probably by the formation of L-sorbose 1-phosphate, which inhibits hexokinase.74-75... 

Figure 30. A medium complexity model of yeast glycolysis [342], The model consists of nine metabolites and nine reactions. The main regulatory step is the phosphofructokinase (PFK), combined with the hexokinase (HK) reaction into a single reaction vi. As in the minimal model, we only consider the inhibition by its substrate ATP, although PFK is known to have several effectors. External glucose (Glc ) and ethanol (EtOH) are assumed to be constant. Additional abbreviations Glucose (Glc), fructose 1,6 biphosphate (FBP), pool of triosephosphates (TP), 1,3 biphosphogly cerate (BPG), and the pool of pyruvate and acetaldehyde (Pyr).

Many examples of product inhibition are to found. Some dehydrogenases are inhibited by NADH (a co-product of the reaction), e.g. PDH and isocitrate dehydrogenase (ICD), which are involved with the glycolysis and the TCA cycle are two such examples. Hexokinase isoenzymes in muscle (but not liver) and citrate synthase are inhibited by their products, glucose-6-phosphate and citrate respectively offering a very immediate fine tuning of reaction rate to match cellular requirements and possibly allowing their substrates to be used in alternative pathways. 

GNG exploits the fact that most of the reactions of glycolysis are reversible so the enzymes are shared between the two pathways. There are three kinase reactions (glucokinase/hexokinase, PFK and pyruvate kinase), which are not physiologically reversible are therefore the problem steps in the synthesis of glucose these three steps are overcome using alternative enzymes (Table 6.5, see also Section 1.7.1). 

Two examples are presented the hexokinase and phos-phoglucoisomerase reaction in glycolysis (data taken from experiments with the isolated perfused rat heart). 

The large and negative value for hexokinase indicates that this enzyme catalyses the reaction only in the direction of glucose 6-phosphate formation, i.e. it is a non-equilibrium reaction in vivo. In contrast, the low value for phosphoglucoisomerase indicates that it is a reaction that is close to equilibrium in vivo, that is, it can proceed in either direction. AG valnes for all the reactions of glycolysis indicate that those catalysed by hexokinase, phosphorylase, phos-phofractokinase and pyrnvate kinase are non-eqnilibrinm the others are near eqnilibrinm (Fignre 2.6). 

Figure 2.6 The process of glycolysis illustrating the three non-eguilibrium reactions. The reactions are catalysed by hexokinase, phosphofructokinase and pyruvate kinase which are indicated by the heavy unidirectional arrows. The reactions in which ATP is utilised and those in which it is produced are indicated (see Appendix 2.7).

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