Lethal synthesis, or suicide metabolism, is the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

of a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

from a precursor which is not itself toxic, such as the synthesis of

fluorocitrate Fluorocitric acid is a fluorinated carboxylic acid derived from citric acid by substitution of one hydrogen by a fluorine atom. The appropriate anion is called fluorocitrate. Fluorocitrate is formed in two steps from fluoroacetate. Fluoroacetate i ...

from

fluoroacetate Fluoroacetate may refer to: * Fluoroacetic acid * Sodium fluoroacetate Sodium fluoroacetate is an organofluorine chemical compound with the formula FCH2CO2Na. This colourless salt has a taste similar to that of sodium chloride and is used as a r ...

or the synthesis of

methylglyoxal Methylglyoxal (MGO) is the organic compound with the formula CH3C(O)CHO. It is a reduced derivative of pyruvic acid. It is a reactive compound that is implicated in the biology of diabetes. Methylglyoxal is produced industrially by degradation ...

from

glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...

. The term was first publicised by

Rudolph Peters Sir Rudolph Albert Peters MC MID FRS H FRSE FRCP LLD (13 April 1889 – 29 January 1982) was a British biochemist. He led the research team at Oxford who developed British Anti-Lewisite (BAL), an antidote for the chemical warfare agent lewisite ...

in his

Croonian Lecture The Croonian Medal and Lecture is a prestigious award, a medal, and lecture given at the invitation of the Royal Society and the Royal College of Physicians. Among the papers of William Croone at his death in 1684, was a plan to endow a single l ...

of 1951.

Lethal Synthesis of Methylglyoxal

A 1971 study published by the

Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

identified

, a form of glycerol, as a product of lethal synthesis in a specific ''E.coli''

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

. In ''E.coli,'' the synthesis of triose

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

from

is a reaction regulated by the synthesis rate of

glycerol kinase Glycerol kinase, encoded by the gene ''GK'', is a phosphotransferase enzyme involved in triglycerides and glycerophospholipids synthesis. Glycerol kinase catalyzes the transfer of a phosphate from ATP to glycerol thus forming glycerol 3-phosph ...

and by

feedback inhibition An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

fructose-1,6-bisphosphate Fructose 1,6-bisphosphate, also known as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6 (i.e., is a fructosephosphate). The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructos ...

. The study demonstrated that, in ''E.coli'' mutants that had lost both control mechanisms, glycerol kinase no longer reacted to feedback regulation and instead produced the

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

methylglyoxal. A more recent review of research done on methylglyoxal

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

concluded that the compound's cytotoxic nature is dependent on its ability to form advanced

glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...

end products (AGEs). These compounds, which are thought to be factors in ageing and in the progression of

degenerative disease Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time. In neurodegenerative diseases, cells of the central nervous system stop wor ...

s, have been shown to hinder the functions of the proteins they target.

References

Metabolism Toxins {{biochem-stub