D-glucuronic Acid

Glucuronic acid (from Greek γλεῦκος "''wine, must''" and οὖρον "''urine''") is a uronic acid that was first isolated from urine (hence the name). It is found in many gums such as gum arabic (c. 18%), xanthan, and kombucha tea and is important for the metabolism of microorganisms, plants and animals.

Properties

Glucuronic acid is a sugar acid derived from glucose, with its sixth carbon atom oxidized to a carboxylic acid. In living beings, this primary oxidation occurs with UDP-α-D-glucose (UDPG), not with the free sugar.

Glucuronic acid, like its precursor glucose, can exist as a linear (carboxo-)aldohexose (<1%), or as a cyclic hemiacetal ( furanose or pyranose). Aldohexoses such as D-glucose are capable of forming two furanose forms (α and β) and two pyranose forms (α and β). By the Fischer convention, glucuronic acid has two stereoisomers (enantiomers), D- and L-glucuronic acid, depending on its configuration at C-5. Most physiological sugars are of the D-configuration. Due to ring closure, cyclic sugars have another asymmetric carbon atom (C-1), resulting in two more stereoisomers, named anomers. Depending on the configuration at C-1, there are two anomers of glucuronic acid, α- and β-form. In β-D-glucuronic acid the C-1 hydroxy group is on the same side of the pyranose ring as the carboxyl group. In the free sugar acid, the β-form is prevalent (~64%), whereas in the organism, the α-form UDP-α-D-glucuronic acid (UDPGA) predominates.

Carbohydrate stereoisomers, which differ in configuration at only one (other) asymmetric C-atom, are named epimers. For example, D-mannuronic (C-2), D-alluronic (C-3), D-galacturonic (C-4), and L-iduronic acid (C-5) are epimers of glucuronic acid.

The nonplanar pyranose rings can assume either chair (in 2 variants) or boat conformation. The preferred conformation depends on spatial interference or other interactions of the substituents. The pyranose form of D-glucose and its derivative D-glucuronic acid prefer the chair ⁴C₁.

Additional oxidation at C-1 to the carboxyl level yields the dicarboxylic glucaric acid is the self-ester (lactone) of glucuronic acid.

Direct oxidation of an aldose affects the aldehyde group first. A laboratory synthesis of a uronic acid from an aldose requires protecting the aldehyde and hydroxy groups from oxidation, for example by conversion to cyclic acetals (e. g., acetonides).

Sodium glucuronate can be produced by the direct oxidation of starch with concentrated nitric acid. In this preparation the low availability of water keeps the starch polymers from hydrolyzing and only oxidizes the free hydroxyls, in much the same way that nitrogen dioxide would oxidize the starch. Once this reaction is complete, and the starch/nitric acid mix turns clear (after giving off nitrogen dioxide gas), the solution can be diluted, and hydrolyzed with another mineral acid. Then the oxidation is slowly quenched with sodium hydroxide (or sodium bicarbonate), forming sodium glucuronate, which can be crystallized out of solution. With transition metals, it forms complexes such as iron(III) glucuronate, iron(II) glucuronate, and copper(II) glucuronate.

Functions

Proteoglycans

Glucuronic acid is a common building block of proteoglycans and glycoglycerolipids:
* Heparin is an inhibitor of blood coagulation, and occurs in mast cells, lung and liver.
* Chondroitin sulfate is found in large quantities in cartilage, aorta, connective tissue, bone, and skin.
* Dermatan sulfate is a proteoglycan in skin, heart, and blood vessels.
* Keratan sulfate is found in the cornea, cartilage, and bone.
* Hyaluronic acid occurs in large quantities in connective tissues, skin, cartilage, and synovial fluid.
* Glycoglycerolipids of glucuronic or galacturonic acids form the cell walls of bacteria.

Glucuronidation

UDP-α-D-glucuronic acid (UDPGA) is often involved in the phase II metabolism (conjugation) of lipophilic xeno- and endobiotic