Uronic acid pathway

L-Xylulose Intermediate in uronic acid pathway. 1 I Found in urine in essential pentosuria. 

GLUCURONATE, A PRECURSOR OF PROTEOGLYCANS CONJUGATED GLUCURONIDES, IS A PRODUCT OF THE URONIC ACID PATHWAY... 

Disruption of the Uronic Acid Pathway Is Caused by Enzyme Defects Some Drugs... 

The uronic acid pathway is the source of glucuronic acid for conjugation of many endogenous and exogenous substances before excretion as glucuronides in urine and bile. 

Vitamin C (Figure 45-19) is a vitamin for human beings and other primates, the guinea pig, bats, passerine birds, and most fishes and invertebrates other animals synthesize it as an intermediate in the uronic acid pathway of glucose metabohsm (Chapter 20). In those species for which it is a vitamin, there is a block in that pathway due to absence of gulonolactone oxidase. Both ascorbic acid and dehydroascorbic acid have vitamin activity. 

Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates, thus making ascorbic acid an essential in the diet. 

It has been shown that UDP-D-galacturonic acid is present in higher plants (32) and that they contain enzymes which lead to the formation of this uronic acid nucleotide, starting with UDP-D-glucose by the following pathway (33, 34) ... 

The use of bromine in alkaline media resulted in the formation of uronic acids.416,417 Oxidation to some non-uronic acid products, (carbonyl compounds) accompanied the major oxidation pathway.418-420 The 2,2,6,6-tetramethyl-l-piperidinyloxy-mediated oxidation by hypobromite was highly selective for the 6-OH groups of the glucose residues.421 Potassium bromate (HB1-O3) was also used.338 The kinetics of oxidation with bromine at pH 6-8 has been studied 422 It was observed that oxidation decreases the heat and temperature of gelation as the oxidation proceeds. Simultaneously, the molecular weight of starch and the viscosity of its aqueous solutions decreased. Subsequent reduction of the oxidation products increased the viscosity. Microscopic observations revealed that the starch granularity vanished at a low level of oxidation.423... 

A nucleoside pyrophosphoric ester of this uronic acid, UDP-d-galacturonic acid, was shown to be present in mung beans. " In this plant were also found enzymes that led to the formation of this uronic acid derivative of a nucleoside pyrophosphate by the following pathway ... 

The series A-K represents fundamental modes of fragmentation for all glycosides. Substituents, or such modifications as the introduction of deoxy (methylene) groupings or acetamido functions, can alter the relative importance of particular series of fragments. Furanoid sugars, anhydro sugars, and uronic acid derivatives follow the same, major, breakdown pathways. 

Uronic acid azides constitute important precursors for A -glycosyl amino acids and their various peptide derivatives, and may be formed by a comparable pathway. Thus, the treatment of acetyl-protected uronic acid esters with tri-methylsilyl azide and SnCU gives the desired acetylated 1,2-trans methyl (o-glycopyranosyl azide)uronates in crystalline form. " Whereas the yields for the gluco 61 and galacto derivatives 62 are satisfactory, the manno analog 63 was obtained in only 11 % yield. Even with an excess of trimethylsilyl azide, the results could not be improved. ... 

Sugar skeletons are interconverted by way of three classes of compound, sugar phosphates, sugar nucleotides and cyclitols and the major known pathways which interconnect them are summarised in the schemes later in this chapter. The sugar nucleotides are the main intermediates in these interconversions and it is their metabolism which forms the bulk of this chapter. The cyclitols provide an important and, sometimes, dominant route from hexose to uronic acid and, thence, pentoses in plants, but their role in animals is unclear. Sugar phosphates are of importance as the entry to the sugar nucleotide pathways, but of themselves contribute little to metabolic interconversion directly for anabolic purposes. 

Whereas there is good evidence that this pathway is an important route to uronic acids and pentoses in many plant tissues (Rubery and Northcote, 1970) — and is often the dominant route — its importance in animal tissues is uncertain. 

Potentially the cyclitol pathway could be more elaborate, with various epimerisation or substitutions occurring at the cyclitol level and not by way of sugar nucleotides. As Loewus has pointed out, any blockade at C-1 of myoinositol would eventually prevent decarboxylation of the uronic acid and pentose formation, while allowing UDPGalA to form. However, there is little evidence directly for or against such mechanisms. Nevertheless, the cyclitol pathway is extremely important as a major route and part of a potential regulatory system in plants, as the evidence of Rubery and Northcote (1970) shows (see Chapter 5). 

Figure 2.11 The Metabolism of UDP Hexoses and Pentoses. Similar pathways have been proposed for TDP sugars (Figure 2.14), save that the dehydrogenase reaction to generate uronic acid may be NADP-, not NAD-, dependent.

---