Salicylhydroxamic acid
Encyclopedia
Salicylhydroxamic acid (SHA or SHAM) is a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 that is a potent and irreversible inhibitor of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

l and plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

 urease
Urease
Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926, James Sumner showed that urease is a protein. Urease is found in bacteria, yeast, and several higher plants. The structure of urease was first solved by P.A...

 usually used for urinary tract infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. The molecule is similar to urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

 but is not hydrolyzable by the urease enzyme. It is also a trypanocidal agent
Trypanocidal agent
A trypanocidal agent is an antiprotozoal agent that acts upon on trypanosome parasites.Examples include:* benzonidazole* blasticidin S* DAPI* diminazene* diminazene aceturate* eflornithine* ethidium* isometamidium chloride* lonidamine...

. When administered oral
Oral administration
Oral administration is a route of administration where a substance is taken through the mouth.-Terminology:Per os is an adverbial phrase meaning literally from Latin "by mouth" or "by way of the mouth." The expression is used in medicine to describe a treatment that is taken orally. The...

ly, it is metabolized to salicylamide
Salicylamide
Salicylamide is the common name for the substance o-hydroxybenzamide, or amide of salicyl. Salicylamide is a non-prescription drug with analgesic and antipyretic properties. Its medicinal uses are similar to those of aspirin. Salicylamide is used in combination with both aspirin and caffeine in...

 which exerts analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

, antipyretic
Antipyretic
Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...

 and antiinflammatory effects.

Salicylhydroxamic acid is also a common ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

 utilized in the synthesis of metallacrown
Metallacrown
thumb|300px|right|Figure showing the metallacrown analogy to the organic crown ether. Ligand substituents are omitted for clarity. a) 12-crown-4 b)12-MCFeN-4 c) 15-crown-5 d) 15-MCCuN-5...

s.

In plants, some fungi and some protists with the alternative oxidase
Alternative oxidase
The alternative oxidase is an enzyme that forms part of the electron transport chain in plants, as well as some fungi, protists and possibly some animals. Sequences similar to the plant oxidase have also been identified in bacterial genomes....

 (AOX) enzyme in the mitochondrial electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...

 system, salicylhdroxamic acid acts as an inhibitor of the enzyme, blocking the largely uninhibited flow of electrons through AOX. AOX acts as a "short circuit" of the normal electron chain, dissipating electrons with a much-decreased translocation of protons, and therefore diminished production of ATP by oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

. When AOX is blocked by SHAM, electrons are forced through the cytochrome pathway and through cytochrome IV, allowing observation of the operation of the cytochrome pathway without AOX activity. The AOX pathway is found to be the exclusive electorn transport pathway in Trypanosoma brucei
Trypanosoma brucei
Trypanosoma brucei is a parasitic protist species that causes African trypanosomiasis in humans and nagana in animals in Africa. There are 3 sub-species of T. brucei: T. b. brucei, T. b. gambiense and T. b. rhodesiense.These obligate parasites have two hosts - an insect vector and mammalian host...

- the organism that causes African Sleeping Sickness, meaning that SHAM completely shuts down energy production in this organism.
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