A glucuronide, also known as glucuronoside, is any substance produced by linking

glucuronic acid Glucuronic acid (GCA, from ) is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many natural gum, gums such as gum arabic ( 18%), xanthan, and kombucha tea and is important for the metabolism of ...

to another substance via a

glycosidic bond A glycosidic bond or glycosidic linkage is a type of ether bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal group o ...

. The glucuronides belong to the

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

Glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

, the conversion of chemical compounds to glucuronides, is a method that animals use to assist in the excretion of toxic substances, drugs or other substances that cannot be used as an

energy Energy () is the physical quantity, quantitative physical property, property that is transferred to a physical body, body or to a physical system, recognizable in the performance of Work (thermodynamics), work and in the form of heat and l ...

source. Glucuronic acid is attached via a glycosidic bond to the substance, and the resulting glucuronide, which has a much higher water

solubility In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...

than the original substance, is eventually excreted by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s. Enzymes that cleave the glycosidic bond of a glucuronide are called glucuronidases.

Classes of glucuronides

Acyl glucuronide

Carboxylic acids In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

are a common functional group in many medications, such as NSAIDS,

anticonvulsants Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatment ...

, and

diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

. One common pathway for the clearance of carboxylic-acid-containing drugs is via glucuronidation. By conjugating one such drug to a glucuronide, the resulting compound should be less toxic and exhibit rapid clearance from the body. Many ''in vitro'' studies have provided compelling evidence to suggest, however, that acyl glucuronidation could have adverse pharmalogical effects due to protein adduction. Two mechanisms in which acyl glucuronides lead to protein adduction are: transacylation of the 1-O-β-glucuronide and glycation of the 3-O-β-glucuronide.

N⁺-glucuronide

Glucuronidation of nitrogen-containing compounds generally form quaternary ammonium-linked glucuronides.

Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

, which contains a pyridine ring and a pyrrolidine ring, is conjugated at the pyridine nitrogen during drug metabolism. There are two enantiomers of nicotine: S(-)-nicotine and R(+)-nicotine. S(-)-nicotine is the more common stereoisomer of the compound, primarily forming through combustion of nicotine-containing drugs. The S(-)-nicotine ''N1''-glucuronide has a lower K_m and higher V_max for liver microsomes than the N(+)-nicotine ''N1''-glucuronide, suggesting that the body has evolved to favor the eradication of the more common N-linked moiety

Examples

* Miquelianin (

Quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...

3-O-glucuronide) *

Morphine-6-glucuronide Morphine-6-glucuronide (M6G) is a major active metabolite of morphine. M6G is formed from morphine by the enzyme UGT2B7. It has analgesic effects roughly half that of morphine. M6G can accumulate to toxic levels in kidney failure. History of di ...

* Scutellarein-7-glucuronide

References

Toxicology {{med-toxic-stub

Classes of glucuronides

Acyl glucuronide

N+-glucuronide

Examples

References

N⁺-glucuronide