Enzyme inhibitors cyanide

Enzyme inhibitors are broadly classified as irreversible and reversible. Inhibitors of the first class usually cause an inactivating, covalent modification of enzyme structure. Cyanide is a classic example of an irreversible enzyme inhibitor. The kinetic effect of irreversible inhibitors is to decrease the concentration of active enzyme. Irreversible inhibitors are usually considered to be poisons and are generally unsuitable for therapeutic purposes. 

Even the controversial cyanic anticancer substance known as laetrile, or amygda-lin, is thought to be detoxified by a particular enzyme or enzymes in normal cells that is not ordinarily present, or in sufficient concentrations, in cancer cells. The answer is not clear-cut, however, and laetrile remains suspect, if effective at all. More than this, there are certain other food enzymes that may cause laetrile to give off deadly hydrogen cyanide or hydrocyanic acid, or HCN, itself an enzyme inhibitor that acts against bodily processes, notably respiration. (Deadly cyanide, incidentally, is listed as an inhibitor for tyrosinase, the enzyme involved in melanoma.)... 

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. 

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. 

In all H2ases, the Fe center is coordinated to carbonyl and cyanide ligands. Both ligands are ubiquitous in inorganic chemistry. Equally well, they are highly toxic and in fact strong enzyme inhibitors, for example, for Fe-containing... 

The cyanide ion (CN ) is an example of an irreversible enzyme inhibitor. It is extremely toxic and acts very rapidly. The cyanide ion interferes with the operation of an iron-containing enzyme called cytochrome oxidase. The ability of cells to use oxygen depends on the action of cytochrome oxidase. When the cyanide ion reacts with the iron of this enzyme, it forms a very stable complex (Reaction 10.8), and the enzyme can no longer function properly. As a result, cell respiration stops, causing death in a matter of minutes. 

Most powerful poisons are lethal because they inhibit enzymes required for life. Hydrogen cyanide and hydrogen sulfide liberate ions, CN" and HS . that combine with ferric iron atoms in the cytochromes, which are heme enzymes that catalyze the cellular oxidation reactions required for life. Many drugs are enzyme inhibitors. 

Biological catalysts are known as enzymes (Chapter 23 on the accompanying website) and consist of proteins, often associated with metal ions. A substance that decreases the rate of a reaction is called an inhibitor. An example of an inhibitor is the anti-knock compound, tetraethyl lead(iv), which was used to prevent pre-ignition in leaded petrol vapour but has now been banned in practically all countries (Chapter 10). There are many specific and general inhibitors known for enzymes many nerve gases and poisons, for example cyanides, operate as enzyme inhibitors, often by interacting with the active site of the enzyme (Figure 6.13). 

Monoamines as substrates for diamine oxidase. There have been reports in the literature of the oxidation by diamine oxidase preparations of varying degrees of purity, of compounds which previously were recognized as typical substrates for monoamine oxidase only (117-119). The rates of oxidation of the monoamine substrates in these instances were usually lower than those for the diamines. In addition the enzyme preparations showed the expected susceptibility to typical diamine oxidase inhibitors (cyanide, carbonyl reagents, etc.). As a result of such studies it seemed that a new type of amine oxidase had been discovered. The status of this problem is at present unclear. 

When blood is previously treated with dilute cyanide or other appropriate enzyme inhibitors, and then exposed to a vacuum, the amoimt of rapidly-released carbon dioxide is greatly but not entirely diminished, whereas the slowly-released carbon dioxide is unaffected. 

Another type of inhibitor combines with the enzyme at a site which is often different from the substrate-binding site and as a result will inhibit the formation of the product by the breakdown of the normal enzyme-substrate complex. Such non-competitive inhibition is not reversed by the addition of excess substrate and generally the inhibitor shows no structural similarity to the substrate. Kinetic studies reveal a reduced value for the maximum activity of the enzyme but an unaltered value for the Michaelis constant (Figure 8.7). There are many examples of non-competitive inhibitors, many of which are regarded as poisons because of the crucial role of the inhibited enzyme. Cyanide ions, for instance, inhibit any enzyme in which either an iron or copper ion is part of the active site or prosthetic group, e.g. cytochrome c oxidase (EC 1.9.3.1). 

Inhibitors may act reversibly or irreversibly to limit the activity of the enzyme. Irreversible inhibitors are enzyme poisons and indeed many of them are poisonous in the common sense of the word cyanide for example, is an irreversible inhibitor of one of the cytochromes in oxidative phosphorylation. 

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