Enzymatic formation of uridine

Many studies have shown that, although glucose is converted to glucuronides without cleavage of the carbon chain (2--S), free glucuronic acid functions poorly, if at all, as a precursor of glucuronic acid-containing compounds in living systems (e.g. phenol or alcohol glucuronides, mucopolysaccharides) (9-l 1). An important advance in elucidating the nature of the intermediates in the biosynthesis of glucuronic acid and its conjugates was made when Dutton and Storey discovered a thermostable cofactor in liver necessary for the formation of a phenol glucuronide by cell-free liver preparations (12). This compound was subsequently isolated and identified as uridine diphosphoglucuronic acid (13-15), and was shown to act as a substrate in a reaction in which glucuronic acid was transferred to a suitable acceptor with the formation of a glucuronide. The biosynthesis of this nucleotide might take place through various pathways. Kornberg (16) first showed that the synthesis of oxidized diphosphopyridine nucleotide’ occurred via a reaction between adenosine triphosphate and nicotinamide mononucleotide with the formation of the nonsymmetrical pyrophosphate nucleotide and inorganic pyrophosphate. This type of mechanism has also been found to be operative in the synthesis of uridine diphosphoglucose (17) (Equation 1) and other nucleotides.