Phosphate-metabolizing inhibition

Li+ causes malformation and affects regeneration in some protozoans, for example Tetrahymenapyriformis [231], by inhibiting both DNA and RNA synthesis by affecting regeneration in Hydra [232], planarians [233], and annelids [234] and by affecting cell signaling mediated by both inositol phosphate metabolism [235] and adenylate cyclase [236] in slime molds. 

An additional action of Li" is interruption of the phosphatidylinositide cycle through an inhibitory action on inositol phosphate metabolism. By this mechanism, depletion of membrane inositol and the phosphoinosi-tide-derived second-messenger products diacylglycerol and inositol triphosphate ultimately reduces signaling through receptor systems dependent on the formation of these products. It is presently unclear to what extent inhibition of inositol phosphate metabolism contributes to the therapeutic properties of Li+ in bipolar patients. 

Inhibition of Phosphate-Metabolizing Enzymes by Vanadium Compounds... 

Both 27Al and 31P NMR have been used to study the uptake of Al3+ by cell suspensions of the alga Chlorella saccaraphila (Folsom et al., 1986). The results were interpreted as indicating Al complexation with cytoplasmic phosphates, and inhibition of glucose metabolism. 

Figure 9-1 Sites of feedback inhibition in carbamyl phosphate metabolism of E. coli. Note that aspartate trascarbamylase is the first enzyme on the unique pathway to pyrimidine compounds.

AT-Acetyl-D-glucosamine 6-phosphate is metabolized to the D-fructose ester more slowly (by preparations of kidney enzyme) than is D-glucosamine 6-phosphate/ Acetate inhibits the disappearance of AT-acetyl-n-glucos-amine 6-phosphate, but does not affect the disappearance of D-glucosamine 6-phosphate. A possible sequence of reactions for these transformations is as follows. ... 

Chemically and enzymatically stable diphosphonates are commonly used in treatment of various diseases of bone and calcium metabolism. They bind strongly to calcium phosphate and inhibit its formation, aggregation, and dissolution. The affinity for the bone mineral is the basis for their use as skeletal markers and inhibitors of bone resorption. " ... 

Cestodes have generally responded well to niclosamide (NC, Nicloside) (Table 7-10). This salicylanilide is highly curative of all four species of tapeworms that depend on anaerobic metabolism for most of their energy. That means that their mitochondria form ATP by incorporating it from inorganic phosphate. NC inhibits this reaction at low concentrations. The classic anaerobic phosphorylation in mammalian cells would also be uncoupled, but at... 

Many enzymes are dependent on dissociable metal ions for their activity, and the operation of most of the important metabolic systems thus requires the presence of these cofactors. For example, the list of enzymes requiring Mg is a long one and includes the oxidases and decarboxylases for the keto acids, most of the enzymes involved in phosphate metabolism, some dehydrogenases, some peptidases, phosphoglucomutase and enolase. These enzymes may be inhibited with inhibitors forming stable complexes with Mg ions. For example, malonate and other dicarboxylic compounds are able to chelate effectively with Mg" and other metal ions, and their inhibition may result from the reduction of metal ion concentration in the medium or the removal of the metal ions from the enzyme [3] ... 

In addition to acting as an inhibitor of dynein and (Na, K)-ATPase, vanadium is also a potent inhibitor of RNase (57) and alkaline and acid phosphatases (58.59). This suggests that vanadium generally tends to inhibit enzymes of phosphate metabolism. However, according to Gibbons et al. (53), the mechanism of Inhibition is not the same in each enzyme. The Inhibition of RNase and alkaline phosphatase is greater by oxyvanadium (IV) than by vanadium (V). 

Boric acid (H3B03,E284) and disodium tetraborate (Na2B407), known as borax (E285) are permitted for use as preservatives in some countries and in the EU are only approved to preserve caviar. Their preservative effect is based on inhibition of decarboxylases of amino acids and inhibition of phosphate metabolism. 

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