This pathway consists of two major interconversions, those of pentose and those of glucuronate. A pentose is an important monosaccharide involved in amino sugar and nucleotide sugar metabolism, the pentose phosphate pathway, and more biochemically relevant synthesis pathways. Glucuronate (D-glucuronic acid) is a carboxylic acid that is highly soluble in water and can link to many compounds in transport and elimination processes (glucuronidation). Its metabolic pathway begins with glucose 1-phosphate (G1P, a naturally occurring Cori ester consisting of a glucose molecule with a phosphate group on the 1'-carbon) from glycolysis. G1P is converted to uridine diphosphate glucose (UDP-glucose) via a reaction catalysed by a transferase enzyme. UDP-Glucose can also enter this pathway from galactose metabolism. An oxidoreductase then catalyses the conversion of UDP-glucose into UDP-glucuronate, which can form a glucuronide via a glucuronosyltransferase-catalysed reaction. In fruit fly glucuronate interconversion, there is one bidirectional enzyme characterized (EC 2.4.1.17, experimental evidence in UniProt) that converts UDP-glucuronate into beta-D-glucuronoside and two experimental enzymes that catalyse the reaction of UDP-glucuronate into D-glucuronate 1-phosphate (the latter two are not included in this pathway for brevity). A beta-glucuronidase then catalyses the conversion of beta-D-glucuronoside into glucuronic acid, which can either feed into inositol phosphate metabolism or be converted into L-gulonate in a reaction aided by NADP-dependent alcohol dehydrogenase. L-Gulonate is converted into 3-dehydro-L-gulonate via an oxideoreducatase-catalysed reaction, which can then form L-xylulose in a reaction involving an unknown enzyme. This ketose can feed into amino sugar and nucleotide sugar metabolism once converted into L-arabitol and subsequently into L-arabinose. Arabinose also feeds into ribulose formation. Pentose interconversion (via L-ribulose) is inferred but not yet characterized in Drosophila melanogaster (see KEGG for pathway details). Alternatively, xylulose, upon conversion into xylitol in a reaction catalysed by L-xylulose reductase, can feed into pentose interconversion, the pentose phosphate pathway, and pyruvate production. Currently, many enzymes involved in pentose interconversion have yet to be characterized in the common fruit fly, but its metabolites feed into the TCA Cycle, among other metabolic pathways, including those of glucuronate interconversion. One such compound is D-xylonolactone, which can both feed into the citrate cycle and produce pyruvate. Another enzyme to note is L-iditol 2-dehydrogenase, which is a widely-distributed enzyme that has been described in archaea, bacteria, yeast, plants and animals. It acts on a number of sugar alcohols, including (but not limited to) L-iditol, D-glucitol, D-xylitol, and D-galactitol. Enzymes from different organisms or tissues display different substrate specificity. The enzyme is specific to NAD+ and cannot use NADP+. In pentose and glucuronate interconversions, this enzyme catalyses the conversion of D-xylitol into D-xylulose. This ketopentose product is then phosphorylated (in a reaction catalysed by xylulokinase), forming xylulose 5-phosphate. The epimerase that converts xylulose 5-phosphate into ribulose 5-phosphate also catalyses the conversion of D-erythrose 4-phosphate into D-erythrulose 4-phosphate and D-threose 4-phosphate. D-Ribulose-5-phosphate feeds into the pentose phosphate pathway. This pathway contains many reversible enzyme-regulated reactions.

Pentose and Glucuronate Interconversions References