The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

Figure 4

Classic path of polyamine metabolism consists of the following: (1) arginine is converted to ornithine through the action of ARG (arginase) in the urea cycle; (2) putrescine is formed from the reaction of ornithine decarboxylation catalyzed by ODC1 (ornithine decarboxylase-1). OAZ can bind to ODC1 to form OAZ-ODC1 complex and subsequently reduce polyamine synthesis. AZIN1 (antizyme inhibitor-1) brakes the ODC1-OAZ complex and liberates ODC1; (3) AMD1 (S-adenosylmethionine decarboxylase) decarboxylates S-adenosylmethionine (SAM) to decarboxylated SAM (dcSAM); (4) dcSAM provides aminopropyl groups to putrescine to produce spermidine by spermidine synthase (SRM) and spermine by spermine synthase (SMS). MTA (methylthioadenosine) is generated as a byproduct. Spermine can be recycled back to spermidine directly by spermine oxidase (SMOX). Spermine and spermidine can be recycled to spermidine and putrescine by spermidine/spermine-N1-acetyltransferase (SAT1) followed by oxidation by polyamine oxidase (PAOX) [101]. MTA can be processed to the methionine: MTA phosphorylase (MTAP) catalyzes the cleavage of MTA yielding 5-methylthioribose-1-phosphate (MTRu-P), which is further metabolized to DHKMP (1,2-dihydro-3-keto-5-methylthiopentene). ADI (acireductone dioxygenase) catalyzes DHKMP to 2-oxo-4-methylthiobutyrate (KMTB) and transamination of KMTB results in formation of methionine [102–104].