With BLASTP 2. 2. 15, mapping now includes NCBI RefSeq concerning database and Ontologies are found in four databases GR, UniProt, UNIPROT and Ref Seq. Ontologies Inhibitors,Modulators,Libraries found in this mapping are much less essentially half of the number found previously in Figure 1. The distribution of evidence codes generated from the bioinformatics based on BLASTP 2. 2. 15 show very different profiles than those of BLASTP 2. 2. 13 of Figure 2. The Sequence Tables, shown in Additional Files 6 and 7, for HepG2 and normal human Liver proteomes, respec tively, are also vastly different from those of BLASTP 2. 2. 13. The catalytic activity DAG of the HepG2 proteome Inhibitors,Modulators,Libraries has five level 2 child nodes transferase, lyase, oxidoreductase, hydrolase and isomerase. Compared to those of BLASTP 2. 2. 13, the DAGs maintain comparatively similar pro files, Seqs and Scores.

Expanded views of the oxidoreductase DAGs are shown in Figure 11. Again, the node filter is fixed at 30 for both HepG2 and liver Inhibitors,Modulators,Libraries DAGs. It is seen that four child nodes are present in HepG2 oxi doreductase node electron carrier activity, disulfide oxidoreductase activity, oxidoreductase activity, acting on CHOOH group of donors, and GO 0016491. The normal liver oxidoreductase has eight child nodes oxidoreductase activity, acting on CH OH group of donors, oxidoreductase activity, acting on paired electron donors, with incorporation or reduction of molecular oxygen, monooxygenase activity, oxidore ductase activity, acting on the aldehyde or oxo group of donors, electron carrier activity, GO 0016491, disulfide oxidoreductase activity, and oxidore ductase activity, acting on CH CH group of donors.

Additional evidence in support of down regulation of oxi doreductases in HepG2 cells are provided by intramolecu lar oxidoreductase activities, shown in Figure 12. The sequences and scores are remarkably similar to the values obtained with BLASTP 2. 2. 13 analyses of Figure 6 HepG2 Liver ]. Discussion Oxidoreductase enzymes are extremely diverse in their structures, Inhibitors,Modulators,Libraries functions, cellular distribution and biochemi cal transformations they mediate. In fact, they are subdi vided into 22 classes, based on the type of biochemical reaction pathway they catalyze. One unique feature of oxidoreductases, however, is that they are strongly down regulated in hepatic neoplasia. The exact reasons and or molecular mechanisms are not known.

Their fun damental roles as mediators of biochemical redox reac tions may offer clues, however, although conclusive empirical evidence is scanty. One Inhibitors,Modulators,Libraries possible clue may be found in the metabolic path ways of purine biosynthesis. kinase inhibitor Oligomycin A In fact, oxidoreductase enzymes that catabolize critical intracellular metabolites of de novo biosynthesis of purines are consistently docu mented to be highly down regulated in hepatomas, the extent of which correlates with the degree and the severity of malignancy and tumor progression.