Inhibitor, glycolysis

Inhibitors may serve any of the several (ten) sequential steps involved in the glycolysis pathway. A partial listing includes certain metallic or mineral substances, notably calcium and magnesium (as the ions Ca and Mg ). These are among the essential minerals found in the diet. Lithium is another inhibitor, which is notably 

It may be added that sulfides or disulfides, which are found to be glycolysis inhibitors, also act as poisons or inhibitors for such inorganic catalysts as nickel or nickel oxide catalysts. 

Various sugars make the listings, denoted by the suffix -ose. Various amino acids also make the listings, denoted by the suffix -ine, notable examples being L-alanine and L-phenylalanine, commonly associated with nutritional supplements. Arginine, an essential amino add (not manufactured in the body), is said to be an inhibitor. The suffix pyridoxal is fisted as an inhibitor, whereby it may be noted that pyridoxine (or pyridoxin) is called vitamin B6. 

Citric acid, found in citrus fruits, is listed as an inhibitor, and also occurs as a reaction intermediate in the metabolic tricarboxylic acid or dtric acid cycle. Ethanol or ethyl alcohol makes an unexpected appearance as an inhibitor, as does glycerol. The ubiquitous alkaloid ingredient of coffee, better known as caffeine, is listed as an inhibitor (in fact, coffee enemas are sometimes used in folkloric cancer treatments). Creatine, a nitrogenous compound found naturally in the body, is an inhibitor, and is a known anticancer agent, for example, as used with urea in a nuxture called Carbatine. 

Fatty acids make the list, especially lauric acid and unsaturated oleic acid. Flavianic acid is a precursor in the preparation of the essential amino acid arginine and the nonessential amino acid tyrosine. Moss (1992) has a chapter about using arginine in the treatment of cancer. Tyrosine interestingly enters the picture as a component of the enzyme tyrosine kinase, the latter in the role of an inhibitor for cancerous stem cells, to be described in Chapter 10. 

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Sodium fluoride is unsuitable as a glycolysis inhibitor its use may lead to incorrectly high glucose concentrations. 

Electric company (Osawa et al., 1981). The membrane developed by Newman (1976) is being used in the 23 A glucose analyzer (Yellow Springs Instrument Co., USA, see Section 5.2.3). Lindh et al. (1982) showed that the cellulose acetate membrane is not truly selective for H2O2, but only decreases the permeation of larger molecules. The sensor was 3 times more sensitive to the glycolysis inhibitor paracetamol than to glucose. The membrane permeability was shown to depend on membrane age. 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

FIGURE 23.11 The principal re mechanisms in glycolysis and glncoi Activators are indicated by plus sign inhibitors by minus signs. 

C5a and C5a des Arg stimulate aerobic glycolysis, hexose monophosphate shunt activity, glucose uptake and the respiratory burst of human neutrophils. All of these processes are stimulated in neutrophil suspensions incubated in the absence of cytochalasin B, but the responses are considerably enhanced if this inhibitor of microtubule assembly is present. Stimulated rates of oxidative metabolism are maximal within 2 min of addition of peptides, with half-maximal responses obtained at 30-60 nM C5a and 1-3 pM C5a des Arg. 

Identification of the energy source for muscle contraction and determination of the order in which the phosphate esters were metabolized was helped by the use of inhibitors. These inhibitors blocked different stages in glycolysis and caused preceding substrates to accumulate in quantities which could greatly exceed those normally present. The compounds were then isolated, identified, and used as specific substrates to identify the enzymes involved in their metabolism. Iodoacetic acid (IAc) was one of the most important inhibitors used to analyze glycolysis. 

Recombinant inhibitors Energy dependence Metabolic activity Glycolysis... 

The above-mentioned procedure for the synthesis of C-fructosides has been used to synthesize the bisphosphono analog of / -D-fructose 2,6-bisphos-phate [ 16], which is, as reported in Sect. 2.3, an important activator of glycolysis and inhibitor of gluconeogenesis. To prepare the target molecule we first attempted the conversion of the firee hy iroxyl group of 21 into an iodide which in turn can be easily converted into a phosphonate. However, this conversion... 

When fructose 2,6-bisphosphate binds to its allosteric site on PFK-1, it increases that enzyme s affinity for its substrate, fructose 6-phosphate, and reduces its affinity for the allosteric inhibitors ATP and citrate. At the physiological concentrations of its substrates ATP and fructose 6-phosphate and of its other positive and negative effectors (ATP, AMP, citrate), PFK-1 is virtually inactive in the absence of fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate activates PFK-1 and stimulates glycolysis in liver and, at the same time, inhibits FBPase-1, thereby slowing gluconeogenesis. 

The same intermediates of glycolysis and the citric acid cycle that activate isocitrate dehydrogenase are allosteric inhibitors of isocitrate lyase. When energy-yielding metabolism is sufficiently fast to keep the concentrations of glycolytic and citric acid cycle intermediates low, isocitrate dehydrogenase is inactivated, the inhibition of isocitrate lyase is relieved, and isocitrate flows into the glyoxylate pathway, to be used in the biosynthesis of carbohydrates, amino acids, and other cellular components. 

The transport system that conveys malate and a-ketoglu-tarate across the inner mitochondrial membrane (see Fig. 19-27) is inhibited by n-butylmalonate. Suppose n-butyl-malonate is added to an aerobic suspension of kidney cells using glucose exclusively as fuel. Predict the effect of this inhibitor on (a) glycolysis, (b) oxygen consumption, (c) lactate formation, and (d) ATP synthesis. 

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