Pathways

Metabolites of Pentobarbital are predicted with biotransformer.

Pentosan polysulfate is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Pentosan polysulfate passes through the liver and is then excreted from the body mainly through the kidney.

Ruta metabólica en la cual se utiliza glucosa para genera ribosa, compuesto necesario para la biosíntesis de ácidos nucleicos.

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.

Pentoses are monosaccharides consisting of five carbon atoms with either aldehyde or ketone functional groups. There are eight stereoisomers of aldopentoses, which include arabinose, lyxose, ribose and xylulose, both D- and L- forms, while there are four for 2-ketopentoses, ribulose and xylulose. Ribose is also very biologically important, as it is one of the three parts of RNA, the others being the phosphate and bases, as well as being related to deoxyribose, one of the major constituents of DNA. In this pathway, CDP-ribitol, the alcohol of pentose with an attached CDP, can be converted to and from D-ribitol 5-phosphate by D-ribitol-5-phosphate cytidylyltransferase, either adding a diphosphate group and removing CTP, or adding CTP and removing the diphosphate. D-ribitol 5-phosphate can then be converted to and from D-ribulose 5-phosphate by ribitol 5-phosphate dehydrogenase, which removes or adds a hydrogen. The protein making up this enzyme is currently unknown in Danio rerio. D-ribulose 5-phosphate can be used in the pentose phosphate pathway, and it can also come from that pathway. It is converted to and from xylulose 5-phosphate by ribulse-phosphate 3-epimerase, and then a phosphate can be removed by xylulokinase to form D-xylulose in another two-way reaction. D-xylulose can then be converted to D-xylitol by sorbitol dehydrogenase, and D-xylitol can be converted to and from D-xylose by an aldehyde reductase. D-xylose can also come into this pathway from starch and sucrose metabolism, and can finally be converted to D-xylono-1,5-lactone by trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, forming one of the end products of this pathway. D-xylitol can also be conveted to and from L-threo-2-pentulose, also known as L-xylulose, by dicarbonyl/L-xylulose reductase, after which the L-thre-2-pentulose can be converted to and from L-arabitol by L-arabinitol 4-dehydrogenase, whose protein is also unknown in Danio rerio. Finally, L-arabitol can be converted to and from L-arabinose by aldose reductase, and L-arabinose can be used in either ascorbate and aldarate metabolism or amino sugar and nucleotide sugar metabolisms, and can also come from ascorbate and aldarate metabolism.

Pentoses are monosaccharides consisting of five carbon atoms with either aldehyde or ketone functional groups. There are eight stereoisomers of aldopentoses, which include arabinose, lyxose, ribose and xylulose, both D- and L- forms, while there are four for 2-ketopentoses, ribulose and xylulose. Ribose is also very biologically important, as it is one of the three parts of RNA, the others being the phosphate and bases, as well as being related to deoxyribose, one of the major constituents of DNA. In this pathway, CDP-ribitol, the alcohol of pentose with an attached CDP, can be converted to and from D-ribitol 5-phosphate by D-ribitol-5-phosphate cytidylyltransferase, either adding a diphosphate group and removing CTP, or adding CTP and removing the diphosphate. D-ribitol 5-phosphate can then be converted to and from D-ribulose 5-phosphate by ribitol 5-phosphate dehydrogenase, which removes or adds a hydrogen. The protein making up this enzyme is currently unknown in Xenopus laevis. D-ribulose 5-phosphate can be used in the pentose phosphate pathway, and it can also come from that pathway. It is converted to and from xylulose 5-phosphate by ribulse-phosphate 3-epimerase, and then a phosphate can be removed by xylulokinase to form D-xylulose in another two-way reaction. D-xylulose can then be converted to D-xylitol by sorbitol dehydrogenase, and D-xylitol can be converted to and from D-xylose by an aldehyde reductase. D-xylose can also come into this pathway from starch and sucrose metabolism, and can finally be converted to D-xylono-1,5-lactone by trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, forming one of the end products of this pathway. D-xylitol can also be conveted to and from L-threo-2-pentulose, also known as L-xylulose, by dicarbonyl/L-xylulose reductase, after which the L-thre-2-pentulose can be converted to and from L-arabitol by L-arabinitol 4-dehydrogenase, whose protein is also unknown in Xenopus laevis. Finally, L-arabitol can be converted to and from L-arabinose by aldose reductase, and L-arabinose can be used in either ascorbate and aldarate metabolism or amino sugar and nucleotide sugar metabolisms, and can also come from ascorbate and aldarate metabolism.

The pentose phosphate pathway—also referred to in the literature as the phosphogluconate pathway, the hexose monophosphate shunt, or the pentose phosphate shunt—is involved in the generation of NADPH as well as pentose sugars. Of the total cytoplasmic NADPH used in biosynthetic reactions, a significant proportion of it is generated through the pentose phosphate pathway. Ribose 5-phosphate is also another essential product generated by this pathway which is employed in nucleotide synthesis. The pentose phosphate pathway is also involved in the digestive process as the products of nucleic acid catabolism can be metabolized through the pathway (pentose sugars are usually yielded in the breakdown) while the carbon backbones of dietary carbohydrates can be converted into glycolytic/gluconeogenic intermediates. The pentose phosphate pathway is interconnected to the glycolysis pathway through the shared use of three intermediates: glucose 6-phosphate, glyceraldehyde 3-phosphate, and fructose 6-phosphate. The pathway can be described as eight distinct reactions (see below) and is separated into an oxidative phase and a non-oxidative phase. Reactions 1-3 form the oxidative phase and generate NADPH and pentose 5-phosphate. Reactions 4-8 form the non-oxidative phase and converts pentose 5-phosphate into other pentose sugars such as ribose 5-phosphate, but generates no NADPH. The eight reactions are as follows: reaction 1 where glucose-6-phosphate 1-dehydrogenase converts glucose 6-phosphate into D-glucono-1,5-lactone 6-phosphate with NADPH formation; reaction 2 where 6-phosphogluconolactonase converts D-glucono-1,5-lactone 6-phosphate into 6-phospho-D-gluconate;reaction 3 where 6-phosophogluconate dehydrogenase converts 6-phospho-D-gluconate into ribulose 5-phosphate with NADPH formation; reaction 4 where ribulose-phosphate 3-epimerase converts ribulose 5-phosphate into xylulose 5-phosphate; reaction 5 where ribose-5-phosphate isomerase converts ribulose 5-phosphate into ribose 5-phosphate; reaction 6 where transketolase rearranges ribose 5-phosphate and xylulose 5-phosphate to form sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate; reaction 7 where transaldolase rearranges of sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate; and reaction 8 where transkelotase rearranges of xylulose 5-phosphate and erythrose 4-phosphate to form glyceraldehyde 3-phosphate and fructose-6-phosphate.