Vanillylmandelic acid (VMA) is a

chemical intermediate In chemistry, a reaction intermediate or an intermediate is a molecular entity that is formed from the reactants (or preceding intermediates) but is consumed in further reactions in stepwise chemical reactions that contain multiple elementary s ...

in the synthesis of artificial vanilla

flavorings A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of the gustato ...

and is an end-stage

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, c ...

of the

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a substi ...

s ( dopamine,

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

, and norepinephrine). It is produced via intermediary metabolites.

Chemical synthesis

VMA synthesis is the first step of a two-step process practiced by Rhodia since the 1970s to synthesize artificial vanilla. Specifically the reaction entails the

condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...

guaiacol Guaiacol () is an organic compound with the formula C6H4(OH)(OCH3). It is a phenolic compound containing an methoxy functional group. Guaiacol appears as a viscous colorless oil, although aged or impure samples are often yellowish. It occurs wi ...

and

glyoxylic acid Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. Str ...

in an ice cold,

aqueous solution An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be ...

with sodium hydroxide.

Biological elimination

VMA is found in the

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. Cellular m ...

, along with other catecholamine metabolites, including

homovanillic acid Homovanillic acid (HVA) is a major catecholamine metabolite that is produced by a consecutive action of monoamine oxidase and catechol-O-methyltransferase on dopamine. Homovanillic acid is used as a reagent to detect oxidative enzymes, and is asso ...

(HVA),

metanephrine Metanephrine ( metadrenaline) is a metabolite of epinephrine (adrenaline) created by action of catechol-O-methyl transferase on epinephrine. An article in the ''Journal of the American Medical Association'', 2002, indicated that the measurement o ...

, and

normetanephrine Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromoc ...

. In timed urine tests the quantity excreted (usually per 24 hours) is assessed along with

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

clearance, and the quantity of

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

s, and

s excreted is also measured. Noradrenaline breakdown

Clinical significance

Urinary VMA is elevated in patients with tumors that secrete catecholamines. These urinalysis tests are used to diagnose an adrenal gland tumor called

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

, a tumor of

-secreting chromaffin cells. These tests may also be used to diagnose neuroblastomas, and to monitor treatment of these conditions. Norepinephrine is metabolised into

and VMA. Norepinephrine is one of the hormones produced by the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

s, which are found on top of the kidneys. These hormones are released into the blood during times of physical or emotional stress, which are factors that may skew the results of the test.

References

{{Tumor markers Neurochemistry Alpha hydroxy acids O-methylated natural phenols Phenolic human metabolites Acetic acids Vanilloids