Glucuronic acid

Glucuronic acid
Other names	β-D-glucopyranuronic acid
Identifiers
CAS number	[6556-12-3]
PubChem	610
MeSH	Glucuronic+acid
SMILES	O[C@H]1[C@H](O)[C@H](O[C@@H](O)[C@@H]1O)C(=O)O
Properties
Molecular formula	C6H10O7
Molar mass	194.14 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references

Glucuronic acid (from Greek γλυκερός - "sweet") is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid. Its formula is C₆H₁₀O₇.

The salts and esters of glucuronic acid are known as glucuronates; the anion C₆H₉O₇⁻ is the glucuronate ion.

Glucuronic acid should not be confused with gluconic acid, a linear carboxylic acid resulting from the oxidation of a different carbon of glucose. Both glucuronic acid and gluconic acid are reported to be found in the fermented drink known as kombucha. Glucuronic acid has been attributed with the mildly-alcoholic effect that drinking the tea has for some.^{[citation needed]}

Functions

Glucuronidation

Glucuronic acid is highly soluble in water. In the animal body, glucuronic acid is often linked to the xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds, and this linkage process is known as glucuronidation.^[1] Glucuronidation occurs mainly in the liver, although the enzyme responsible for its catalysis, UDP-glucuronyltransferase, has been found in all major body organs, e.g., heart, brain, kidneys, adrenal gland, spleen, and thymus.^[2] UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate) is an intermediate in the process and is formed in the liver. One example is this N-glucuronidation of an aromatic amine, 4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver.^[3]

The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water-soluble than the non-glucuronic acid-containing substance from which they were originally synthesised. The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body upon urination. Hormones may also be glucuronidated to allow for easier transport around the body. Pharmacologists also commonly link drugs to glucuronic acid to allow for easier drug delivery.

The conjugation of xenobiotic molecules with hydrophilic molecular species such as glucuronic acid is known as phase II metabolism.

Conformation

The β-D methyl glycoside of glucuronic acid in the low energy ⁴C₁ conformation

Unlike its C5 epimer iduronic acid, which may occur in a number of conformations, glucuronic acid occurs in predominantly the ⁴C₁ conformation.^[4]

Other functions

Polymerized with N-acetylglucosamine it forms hyaluronan.

Glucuronidases

Glucuronidases are those enzymes that hydrolyze the glycosidic bond between glucuronic acid and some other compound.

References

1. ^ King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. doi:10.2174/1389200003339171. PMID 11465080. 
2. ^ Bock K, Köhle C. "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Methods enzymol. 400: 57–75. PMID 16399343. 
3. ^ Al-Zoughool M., Talaska, G. (2006). "4-Aminobiphenyl N-glucuronidation by liver microsomes: optimization of the reaction conditions and characterization of the UDP-glucoronosyltransferase isoforms". J. Appl. Toxicology 26: 524–532. doi:10.1002/jat.1172. 
4. ^ Ferro, D. R. Provasoli, A. (1990). "Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences". Carbohydr. Res. 195: 157–167. doi:10.1016/0008-6215(90)84164-P. PMID 2331699. 

Further reading

• Chiu SH, Huskey SW (1998). "Species differences in N-glucuronidation" (abstract). Drug Metab. Dispos. 26 (9): 838–47. PMID 9733661. http://dmd.aspetjournals.org/cgi/content/abstract/26/9/838. 

• Kuehl GE, Murphy SE (2003). "N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases". Drug Metab. Dispos. 31 (11): 1361–8. doi:10.1124/dmd.31.11.1361. PMID 14570768. 

• Kuehl GE, Murphy SE (2003). "N-glucuronidation of trans-3'-hydroxycotinine by human liver microsomes". Chem. Res. Toxicol. 16 (12): 1502–6. doi:10.1021/tx034173o. PMID 14680362. 

• Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, Jacob P (1999). "Ethnic differences in N-glucuronidation of nicotine and cotinine". J. Pharmacol. Exp. Ther. 291 (3): 1196–203. PMID 10565842. http://www.ucsf.edu/smoking/cgi-bin/cexec/ccompletedprograms/article.pl?issn=973735131. 

• Mannfred A Hollinger, Introduction to Pharmacology, ISBN 0-415-28033-8
• Chang, K. M.; McManus, K.; Greene, J.; Byrd, G. D.; DeBethizy, J. D. Glucuronidation as a metabolic pathway for nicotine metabolism. 1991
• Coffman B.L., King C.D., Rios G.R. and Tephly T.R. The glucuronidation of opioids, other xenobiotics, and androgens by human