Asparagusic acid is an

organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulf ...

with the

molecular formula In chemistry, 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, ...

C₄H₆O₂S₂ and systematically named 1,2-dithiolane-4-carboxylic acid. The molecule consists of a

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

disulfide In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...

(a 1,2- dithiolane) with a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...

side chain. It is found in

asparagus Asparagus, or garden asparagus, folk name sparrow grass, scientific name ''Asparagus officinalis'', is a perennial flowering plant species in the genus '' Asparagus''. Its young shoots are used as a spring vegetable. It was once classified in ...

and is believed to be the metabolic precursor to odorous sulfur compounds responsible for the distinctive smell of

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

which has long been associated with eating asparagus.

Isolation and biosynthesis

The material was originally isolated from an aqueous extract of '' Asparagus officinalis'', a spring

vegetable Vegetables are parts of plants that are consumed by humans or other animals as food. The original meaning is still commonly used and is applied to plants collectively to refer to all edible plant matter, including the edible flower, flowers, ...

. It is a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

of the cyclic

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

1,2- dithiolane with a

bound to carbon-4 of the

heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

Biosynthetic Biosynthesis is a multi-step, enzyme-Catalysis, catalyzed process where substrate (chemistry), substrates are converted into more complex Product (chemistry), products in living organisms. In biosynthesis, simple Chemical compound, compounds are mo ...

studies revealed that asparagusic acid is derived from

isobutyric acid Isobutyric acid, also known as 2-methylpropanoic acid or isobutanoic acid, is a carboxylic acid with structural formula ( CH3)2CH COOH. It is an isomer of ''n''-butyric acid. It is classified as a short-chain fatty acid. Deprotonation or esterif ...

. Asparagusic acid is a colorless solid with a

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depen ...

of 75.7–76.5 °C, higher than that of the corresponding dithiol, dihydroasparagusic acid (or γ,γ-dimercaptoisobutyric acid), at 59.5–60.5 °C.

Laboratory synthesis

A convenient synthesis of asparagusic acid has been developed from a commercially available diethyl malonate derivative starting material, improving on the prior method of Jansen. Diethyl bis(hydroxymethyl)malonate is treated with

hydroiodic acid Hydroiodic acid (or hydriodic acid) is an aqueous solution of hydrogen iodide (HI). It is a strong acid, one that is ionized completely in an aqueous solution. It is colorless. Concentrated solutions are usually 48% to 57% HI. Reactions Hy ...

to yield β,β'-diiodoisobutyric acid after decarboxylation and ester hydrolysis (with removal of volatile

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

and

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is t ...

). Dihydroasparagusic acid, the reduced ( dithiol) form of asparagusic acid, is produced by sequential reaction with sodium

trithiocarbonate Thiocarbonate describes a family of anions with the general chemical formula (''x'' = 0, 1, or 2): *for ''x'' = 2 it is monothiocarbonate ion *for ''x'' = 1 it is dithiocarbonate ion *for ''x'' = 0 it is trithiocarbonate ion Like the carbonate ...

(Na₂CS₃) and

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...

; subsequent oxidation with hot

dimethyl sulfoxide Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...

yields asparagusic acid. : Synthesis of asparagusic acid

Effect on urine

Observations that eating asparagus results in a detectable change in the odour of

have been recorded over time. In 1702, Louis Lémery noted "a powerful and disagreeable smell in the urine", whilst

John Arbuthnot John Arbuthnot FRS (''baptised'' 29 April 1667 – 27 February 1735), often known simply as Dr Arbuthnot, was a Scottish physician, satirist and polymath in London. He is best remembered for his contributions to mathematics, his members ...

noted that "asparagus ... affects the urine with a foetid smell."

Benjamin Franklin Benjamin Franklin ( April 17, 1790) was an American polymath who was active as a writer, scientist, inventor, statesman, diplomat, printer, publisher, and political philosopher. Encyclopædia Britannica, Wood, 2021 Among the leading int ...

described the odour as "disagreable", whilst

Marcel Proust Valentin Louis Georges Eugène Marcel Proust (; ; 10 July 1871 – 18 November 1922) was a French novelist, critic, and essayist who wrote the monumental novel '' In Search of Lost Time'' (''À la recherche du temps perdu''; with the previous ...

claimed that asparagus "transforms my chamber-pot into a flask of perfume." As early as 1891, Marceli Nencki had attributed the smell to

methanethiol Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including humans ...

. The odour is attributed to a mixture of sulfur-containing

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s of asparagusic acid. The origin of asparagus urine is asparagusic acid, a substance unique to this vegetable. Most studies of the compounds responsible for the odour of asparagus urine have correlated the appearance of the compounds above with asparagus consumption; they appear as little as 15 minutes after consumption. However, this does not provide information on the

biochemical processes Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

that lead to their formation. Asparagusic acid and

lipoic acid Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It i ...

are similar in that both possess a 1,2-dithiolane ring with a carboxylic acid tethered to it; indeed, it has been reported that asparagusic acid can substitute for lipoic acid in α-keto-acid oxidation systems such as the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...

. The (''R'')-(+)-

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

of α-lipoic acid is a cofactor in the pyruvate dehydrogenase complex and is essential for aerobic metabolism. The degradation pathway of lipoic acid has been well studied and includes evidence of reduction of the disulfide bridge, ''S''-methylation, and oxidation to produce sulfoxides. Similar transformations of asparagusic acid would lead to metabolites like this detected in asparagus urine. Synthetic work has confirmed the relative ease of oxidation of asparagusic acid to yield ''S''-oxides of the dithiolane ring. The rate of degradation appears highly variably between subjects; the typical

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

for odour disappearance is around 4 h with a between subject variability of 43.4%. In the small minority of people who do not produce these metabolites after consuming asparagus, the reason may be as simple as asparagusic acid not being taken into the body from the digestive tract or that these individuals metabolise it in such a way as to minimise the release of volatile sulfur-containing products.

References

External links

*{{Commons category-inline Asparagus Carboxylic acids Organic disulfides Dithiolanes