Iodoacetic acid is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the

chemical formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...

. It is a derivative of

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...

. It is a toxic compound, because, like many

alkyl halide The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents of hydrogen atom. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalka ...

s, it is an

alkylating agent Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...

. It reacts with

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residues in

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

. It is often used to modify groups to prevent the re-formation of

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

s after the reduction of

cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...

residues to cysteine during

protein sequencing Protein sequencing is the practical process of determining the amino acid sequence of all or part of a protein or peptide. This may serve to identify the protein or characterize its post-translational modifications. Typically, partial sequencing o ...

. In 1929, Dr. Einar Lundsgaard (1899-1968) discovered that

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

poisoned

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

with iodoacetic acid is unable to produce lactate as

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...

from muscle

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

is blocked, causing the muscle to result in an electrically silent contracture. It was remembering this discovery, that lead Dr. Brian McArdle in 1951, to speculate that one of his patients that had electromyographically silent muscle contractures brought on by high-intensity aerobic activity and anaerobic activity must have a defective muscle glycogen mechanism.

Peptidase inhibitor

Iodoacetate is an irreversible

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of all cysteine peptidases, with the mechanism of inhibition occurring from alkylation of the

catalytic Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...

residue (see schematic). In comparison with its amide derivative, iodoacetamide, iodoacetate reacts substantially slower. This observation appears contradictory to standard chemical reactivity, however the presence of a favourable interaction between the positive imidazolium ion of the catalytic histidine and the negatively charged carboxyl-group of the iodoacetic acid is the reason for the increased activity of iodoacetamide.

Possible cancer therapy

Several studies have shown iodoacetate has anti-tumor effects. In 2002 Fawzia Fahim showed that "a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls." In 1975 Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore showed that iodoacetate improved the immune response of bone marrow. In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.

As a disinfection by-product

Iodide An iodide ion is I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine deficiency ...

is a naturally occurring ion that can be found in many source waters and it is easily

oxidized Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

by wastewater disinfectants. One of the products of iodide oxidation is

hypoiodous acid Hypoiodous acid is an inorganic compound with the chemical formula . It forms when an aqueous solution of iodine is treated with mercuric or silver salts. It rapidly decomposes by disproportionation: : Hypoiodous acid is a weak acid with a ...

or hypoiodite (HOI and respectively) which are capable of reacting with background organic materials to generate iodinated

disinfection by-product Disinfection by-products (DBPs) are organic and inorganic compounds resulting from chemical reactions between organic and inorganic substances such as contaminates and chemical treatment disinfection agents, respectively, in water during water di ...

s (DBPs) including iodoacetic acid. In a study performed by Plewa, et al., IAA was determined to be one of the most cytotoxic of those studied, with a

median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. The value of LD50 for a substance is the dose re ...

on the order of magnitude of 10⁻⁵ M. It was the most genotoxic of more than 60 DBPs studied and is the most genotoxic DBP identified thus far. Iodoacetic acid has exhibited traits indicating it as a potential

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

, however, it has not been proven to be carcinogenic. The trend continues in teratogenicity, with iodoacetic acid's potency surpassing that of its brominated and chlorinated analogs. Its toxicity correlates to its ability as an

, which will modify

residues in proteins. Monohaloacetic acids are the most toxic, with toxicity increasing with halogen size. Iodoacetic acid is more toxic than

bromoacetic acid Bromoacetic acid is a chemical compound with the formula . This colorless solid is a relatively strong alkylating agent. Bromoacetic acid and its esters are widely used building blocks in organic synthesis, for example, in pharmaceutical chemistry ...

and much more toxic than

chloroacetic acid Chloroacetic acid, industrially known as monochloroacetic acid (MCA), is the organochlorine compound with the formula . This carboxylic acid is a useful building block in organic synthesis. It is a colorless solid. Related compounds are dichlo ...

References

External links

* The MEROPS online database for peptidases and their inhibitors
Iodoacetate
{{DEFAULTSORT:Iodoacetic Acid Acetic acids Alkylating agents Organoiodides

Peptidase inhibitor

Possible cancer therapy

As a disinfection by-product

References

Further reading

External links