Glucuronic acid

Glucuronic acid
IUPAC name (2S,3S,4S,5R,6R)-3,4,5,6-Tetrahydroxyoxane-2-carboxylic acid
Other names β-D-glucopyranuronic acid
Identifiers
CAS number	6556-12-3 Y
PubChem	441478
ChemSpider	392615 Y
UNII	8A5D83Q4RW Y
DrugBank	DB03156
KEGG	C00191 Y
MeSH	Glucuronic+acid
ChEBI	CHEBI:42717 Y
Jmol-3D images	Image 1
SMILES O=C(O)[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O
InChI InChI=1S/C6H10O7/c7-1-2(8)4(5(10)11)13-6(12)3(1)9/h1-4,6-9,12H,(H,10,11)/t1-,2-,3+,4-,6-/m0/s1 Y Key: AEMOLEFTQBMNLQ-WAXACMCWSA-N Y InChI=1/C6H10O7/c7-1-2(8)4(5(10)11)13-6(12)3(1)9/h1-4,6-9,12H,(H,10,11)/t1-,2-,3+,4-,6-/m0/s1 Key: AEMOLEFTQBMNLQ-WAXACMCWBB
Properties
Molecular formula	C6H10O7
Molar mass	194.14 g mol−1
Melting point	159-161 °C[1]
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Glucuronic acid (from Ancient Greek γλυκός "sweet" + οὖρον "urine") 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.^{[citation needed]}

Functions

Proteoglycans

Glucuronic acid is common in carbohydrate chains of proteoglycans. It is part of mucous animal secretions (such as saliva), cell glycocalyx and intercellular matrix (for instance hyaluronan))

Glucuronidation of toxic substances

Main article: Glucuronidation

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.^[2] 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., intestine, kidneys, brain, adrenal gland, spleen, and thymus.^[3][4]

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 through urine or faeces (via bile from the liver). Hormones may also be glucuronidated to allow for easier transport around the body. Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a broad range of substances. Sometimes toxic substances are also less toxic after glucuronidation.

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

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

Use

Determination of urinary steroids and of steroid conjugates in blood.

Contained in some commercially available brands of Kombucha as an antioxidant & organic acid^[5]

In all plants and mammals-other than guinea pigs and primates-glucuronic acid is a precursor of ascorbic acid, also known as vitamin c^[6] .

Conformation

Unlike its C5 epimer iduronic acid, which may occur in a number of conformations, glucuronic acid occurs in predominantly the ⁴C₁ conformation.^[7]

Glucuronidases

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

Notes

1. ^ D-Glucuronic acid at Sigma-Aldrich
2. ^ King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. doi:10.2174/1389200003339171. PMID 11465080. 
3. ^ Ohno, Shuji; Nakajin, Shizuo (2008-10-06). "Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction". Drug Metabolism and Disposition (American Society for Pharmacology and Experimental Therapeutics) 37 (1): 32–40. doi:10.1124/dmd.108.023598. http://dmd.aspetjournals.org/content/37/1/32.abstract. Retrieved 2010-11-07. 
4. ^ Bock K, Köhle C (2005). "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Methods enzymol. 400: 57–75. doi:10.1016/S0076-6879(05)00004-2. PMID 16399343. 
5. ^ Dave, G.T.. "Ingredients". Ingredients. http://www.synergydrinks.com/enlightened/kombucha_enlightened_multigreen.aspx#. Retrieved 26 August 2011. 
6. ^ Harvey, Richard (2011). Biochemistry (5th Edition). Philadelphia: Wolters Kluwer: Lippincott Williams and Wilkins. pp. 161. ISBN 978-1-60831-412-6. 
7. ^ Ferro, D. R. Provasoli, A. (1990). "Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences". Carbohydr. Res. 195 (2): 157–167. doi:10.1016/0008-6215(90)84164-P. PMID 2331699. 

References

• 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