Enzyme inhibitors fluoride

The activity of the enzyme is also strongly affected by the presence of inhibitors. Fluoride ions inhibit urease (173) and oxalate ions inhibit lactate oxidase (174), but the major inhibitors are heavy-metal ions, such as Ag+, Hg +, Cu " ", organophosphates, and sulfhydryl reagents (/i-chloromercuribenzoate and phenylmercury(II) acetate), which block the free thiol groups of many enzyme active centers, especially oxidase (69). Inhibiting the enzyme electrodes makes it possible to quantify the inhibitors themselves (69), for example, H2S and HCN detection using a cytochrome oxidase immobilized electrode (176). 

Another nucleoside-derived mechanism-based enzyme inhibitor is Fluoronepla-nocin A [79]. This compound is of interest as a broad-spectrum antiviral drug which acts by irreversible inhibition of S-adenosylhomocystein hydrolase (SAH). In a first enzymatic reaction step the 3 -hydroxy group of the inhibitor is oxidized to the corresponding ketone (Scheme 4.34). This leads to depletion of the biochemical oxidizer nicotinamide adenine dinudeotide (NAD ). In the next step a nucleophilic residue of the enzyme undergoes Michael addition to the /i-fluoro a,/>-unsatu-rated ketone moiety. This is followed by fluoride elimination and thus the inhibitor stays covalently trapped in the active site and disables the enzyme permanently. 

Fluoride, in the form of stannous fluoride or tin fluoride, is said to be an enzyme inhibitor that blocks certain critical enzymes in oral bacteria. It is, however, also an inhibitor for other body enzymes, and the organic catalysts that support the myriad biochemical reactions occurring in the body, that is, the bodily functions. The more conventional explanation for fluoride s anticavity action is that it replaces calcium... 

Notable examples of enzyme inhibitors include the many antibiotics that block certain vital funetions in baeteria, but which in controlled doses are not toxic to humans (although there are some antibiotics that are too toxic to use, including some that even kill eaneer eells). Bacterial cells, called prokaryotes, are fortuitously different from mammalian cells, called eukaryotes, and respond differently. The use of fluorides to prevent dental caries is anoth example, the fluorides acting as inhibitors for certain critical enzymes in oral bactraia, as well as facilitating a beneflcial interaction with the dentine at the tooth surfaces. (And, as sometimes warned, if ingested these fluorides can also act as inhibitors for other enzymes within the body.)... 

The inhibition of the enzyme tyrosinase may very well be a key to the control of melanoma, and some of the known inhibitors include eommon substances. Thus, vitamin C, among other common and uncommon substances, has been listed as an enzyme inhibitor for tyrosinase in M.K. Jain s Handbook of Enzyme Inhibitors, 1965-1977 (1982). In addition to ascorbic acid (vitamin C), these other substances include the following halide ion (e.g., from the chloride of common salt, or from iodides and fluorides) butyric acid (from rancid butter) lactic acid (the end product of cancer cell metabolism, found naturally in sour milk products) oxalic acid (ordinarily considered toxic, although it occurs naturally in rhubarb and wood sorrel, etc.) formic acid (a component of ant stings) tyrosine itself and deadly cyanide (which is a chemically bound component of laetrile), as found in almonds (notably bitter almonds), in apricot seeds, and in certain legumes such as beans, etc., although the heat from cooking may drive off the cyanide content. 

The Sigma catalog lists tyrosinase, the enzyme involved in melanoma. As mentioned elsewhere, among the inhibitors listed in the handbooks of enzyme inhibitors are ascorbic acid, or vitamin C, halide ion (the halides being chlorides, notably, but also fluorides, bromides, and iodides), butyric acid (a component of rancid butter), lactic acid (the final product of anaerobic glycolysis, as occurs in cancer cell metabolism, and a component also of sour milk and buttermilk), oxalic acid (e.g., as found in rhubarb and in wood sorrel), formic acid (a component of ant stings), even tyrosine itself, and toxic cyanide ion. And, as has been indicated, alpine sunflower/yueea extract may possibly serve as an enzyme inhibitor for tyrosinase. 

Sometimes a preservative is added to the sample, usually along with an anticoagulant. Sodium fluoride is widely used as a preservative for samples to be analyzed for glucose. This is an enzyme inhibitor that prevents the enzymatic breakdown of glucose, or glycolysis. One milligram sodium fluoride per milliliter blood is adequate. Since it also inhibits other enzymes, including urease, sodium fluoride should not be added to samples to be analyzed for enzymes or for urea based on urease catalysis. 

Enzyme inhibitors are of various types. For example, we can distinguish between irreversible and reversible inhibition. Sometimes an inhibitor reacts so strongly with the active center of an enzyme that the process cannot easily be reversed. Diisopropylfluorophosphate (DFP), for example, undergoes an irreversible reaction with the active centers of certain enzymes, with the liberation of hydrogen fluoride. One of the enzymes with which it reacts is cholinesterase, which is responsible for the functioning of the nerves. As a result DFP is a very powerful nerve gas. Poisons like potassium cyanide exert their action by the irreversible inhibition of enzymes which catalyze oxidative reactions. 

More unusual isosteric replacements for the pwptidic bond were recently proposed (Fig. 13.18). Among them hydroxyethylureas served in the design of a novel class of potent HTV-1 protease inhibitors, diacylcyclopropanes in the design of novel renin inhibitors, and pyrroline-3-ones for various proteolytic enzyme inhibitors. Vinyl fluorides can probably be considered as representing the closest possible bioisosteres of the peptide bond. The synthetic methods available allow, by an appropriate selection of... 

Sodium fluoride is also a reagent in organic chemistry, for instance as a mild fluorinat-ing agent in chlorine - fluorine exchange reactions or as a HF-quencher. Like other Fluorides it has also been employed as an insecticide due to its enzyme inhibitor activity [66]. 

Useful serine/threonine protein phosphatase inhibitors include microcystin-LR (which inhibits protein phosphatases 1, 2A, and 2C, and related enzymes) and /1-glycerophosphate. Sodium fluoride may also be employed. Sodium orthovanadate inhibits protein tyrosine phosphatases. 

In the interaction of isoflurophate with AChE, a phosphorylated intermediate is formed and fluoride is released. An important characteristic of the organophos-phate-induced inhibition is that the bond between the phosphate and the enzyme is very stable. While the regeneration of most carbamylated enzymes occurs with a half-life of minutes or hours, the recovery of a phosphorylated enzyme is generally measured in days. These agents are referred to, therefore, as irreversible inhibitors. 

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