In addition, nucleotide metabolism and salvage path ways have been expanded from previous metabolic models to account for XMP, UMP, GMP, cAMP, and cGMP metabolism. In particular, ATP and GTP can be converted certainly into cAMP and cGMP respectively as adeny late and guanylate cyclases were found to be present in the proteomic data. The erythrocyte uses amino acids to produce glu tathione for redox balancing, converts arginine to polya mines and a byproduct of urea, and utilizes homocysteine for methylation. It has been proposed that Band III is the major methylated protein, particularly for timing cell death. This has also been included in iAB RBC 283. In addition, polyamine metabolism pro duces 5 methylthioadenosine which can be salvaged for methionine recycling.

Another major expansion Inhibitors,Modulators,Libraries in metabolic capabilities represented in iAB RBC 283 is lipid metabolism. Though the mature erythrocyte is unable to produce or degrade fatty acids, the cell can uptake fatty acids from the blood plasma to produce and incorporate diacyl glyercol into phospholipids for upkeep of its membrane. A pseudo carnitine shuttle in the cytosol is used to create a buffer of CoA for the cell. All major ery throcyte fatty acids and phospholi pids are explicitly modeled. The phos phatidylinositols can be converted into various Inhibitors,Modulators,Libraries forms of myo inositols, which play an extensive role in cell sig naling. Finally, FVA showed that the erythrocyte plays an important role in cofactor metabolism. The reconstruc tion accounts for uptake, modification, and secretion of multiple cofactors including vitamin B6, vitamin C, riboflavin, thiamine, heme, and NAD.

Inhibitors,Modulators,Libraries In addition, human erythrocytes play a role in deactivating catecho lamines, hydrolyzing leukotriene, and detoxify ing acetaldehyde which were confirmed in the literature. Metabolite connectivity In order to compare the network structure of the in silico erythrocyte versus other similar metabolic net Inhibitors,Modulators,Libraries works, we calculated the connectivity of each metabolite. Simply, the connectivity is the number of reactions that a metabolite participates in. As a metabolite can be defined as a node in a network structure, the biochem ical reactions associated with a particular metabolite are the edges of the network. Metabolite connectivity thus involves determining the number of edges connected to every node.

We compared the in silico erythrocyte to the global human metabolic Inhibitors,Modulators,Libraries network, Recon 1, as well as the sepa rate human organelles. A dotted line, linking the minimum and maximum connectivities, is drawn on the distributions as a reference Gemcitabine synthesis for comparing the distri butions. A network with higher connectivity would have many points above the dotted line, while lower connec tivity would result in points below the dotted line. Recon 1 has most points above the reference line.