Glycolytic pathway enzymes

The glycolytic pathway enzyme fructose-1,6-bisphosphate aldolase forms an acyl-enzyme intermediate with its ketone substrate fructose 1,6-bisphosphate. Given that the enzyme contains a lysine residue that is essential for its activity, what type of covalent intermediate is likely to be formed ... 

Cell Fractionation Simulation. The wall protein, cytosol and organelles of yeast each contain enzymes which are found nowhere else in the cell. Some examples of these enzymes include invertase in the walls, glycolytic pathway enzymes in the cytosol and fumarase in the mitochondria (13). A model of recovery of these enzymes is offered here. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

For many years hemoglobin was the only allosteric protein whose stereochemical mechanism was understood in detail. However, more recently detailed structural information has been obtained for both the R and the T states of several enzymes as well as one genetic repressor system, the trp-repressor, described in Chapter 8. We will here examine the structural differences between the R and the T states of a key enzyme in the glycolytic pathway, phosphofructokinase. 

In most animal, plant, and microbial cells, the enzyme that phosphorylates glucose is hexokinase. Magnesium ion (Mg ) is required for this reaction, as for the other kinase enzymes in the glycolytic pathway. The true substrate for the hexokinase reaction is MgATP. The apparent K , for glucose of the animal... 

The glycolytic pathway described in this chapter begins with the breakdown of glucose, but other sugars, both simple and complex, can enter the cycle if they can be converted by appropriate enzymes to one of the intermediates of glycolysis. Figure 19.32 shows the mechanisms by which several simple metabolites can enter the glycolytic pathway. Fructose, for example, which is pro-... 

The complete route of gluconeogenesis is shown in Figure 23.1, side by side with the glycolytic pathway. Gluconeogenesis employs three different reactions, catalyzed by three different enzymes, for the three steps of glycolysis that are... 

Acetylcholine is formed from acetyl CoA (produced as a byproduct of the citric acid and glycolytic pathways) and choline (component of membrane lipids) by the enzyme choline acetyltransferase (ChAT). Following release it is degraded in the extracellular space by the enzyme acetylcholinesterase (AChE) to acetate and choline. The formation of acetylcholine is limited by the intracellular concentration of choline, which is determined by the (re)uptake of choline into the nerve ending (Taylor Brown, 1994). 

Inhibitors of several enzymes in the glycolytic pathway, upon which survival of T. brucei is dependent, have been described. Lonidamine (29) has been shown to inhibit T. brucei hexokinase (IC50 = 850 pM) and be toxic to the parasite (T.b. LD50 = 50 pM) in culture [31]. A series of mannitol derivatives have been discovered, which inhibit T. brucei phos-phofructokinase (TbPFK) [32]. The most potent compound (30) within this series exhibits an IC50 = 23 pM in a recombinant enzyme assay and inhibits parasite growth in vitro (IC50 = 30 pM). 

Many enzymes involved in the pathways of intermediary metabolism are Mg2+ dependent, as are a great many of the enzymes involved in nucleic acid metabolism. Of the ten enzymes involved in the glycolytic pathway (see Chapter 5), five are Mg2+ dependent. 

The resting adult human brain consumes around 80 mg of glucose and 50 ml of 02 per minute, and once the glucose has been transported across the plasma membrane it is rapidly phosphorylated by hexokinase, the first enzyme of the glycolytic pathway. Hexokinase... 

A historical note the glycolytic pathway was the very first metabolic pathway to be worked out in detail. This pathway is very well understood, as is each enzyme involved. We shall be concerned with the principal features of the pathway but not with the wealth of detail provided by research in biochemistry over several decades. 

Figure 6.5 Details of the glycolytic pathway. All the enzymes except pyruvate dehydrogenase are present in the cytosol. The pathway, presently the molecular structured of the intermediates, is described in Appendix 6.3.

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