Abstract
Multiple factors involving the methionine salvage pathway (MSP) and polyamine biosynthesis have been found to be involved in cancer cell proliferation, migration, invasion and metastasis. This review summarizes the relationships of the MSP enzyme acireductone dioxygenase (ARD), the ADI1 gene encoding ARD and other gene products (ADI1GP) with carcinomas and carcinogenesis. ARD exhibits structural and functional differences depending upon the metal bound in the active site. In the penultimate step of the MSP, the Fe2+ bound form of ARD catalyzes the on-pathway oxidation of acireductone leading to methionine, whereas Ni2+ bound ARD catalyzes an off-pathway reaction producing methylthiopropionate and carbon monoxide, a biological signaling molecule and anti-apoptotic. The relationship between ADI1GP, MSP and polyamine synthesis are discussed, along with possible role(s) of metal in modulating the cellular behavior of ADI1GP and its interactions with other cellular components.
Highlights
Acireductone dioxygenase (ARD) is a metalloenzyme of the cupin superfamily that is ubiquitous among aerobic cellular organisms
HsARD is encoded by the ADI1 gene, which is located on chromosome 2 at locus 2p25.3 and is comprised of four exons
ADI1GP binding to the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP) regulates the activity of the enzyme towards the intercellular matrix, and reduced ADI1GP levels in tumor cell lines compared with the non-transformed fibroblasts would provide an advantage to the tumor cells for migration and proliferation [17,37,41]
Summary
Acireductone dioxygenase (ARD) is a metalloenzyme of the cupin superfamily that is ubiquitous among aerobic cellular organisms. Subsequent research methionine biosynthesis, but if Ni2+ was bound, an off-pathway reaction occurs, leading to the four residues bound the metal in either case, and the structural differences between the two enzymes are showed that the same four residues bound the metal in either case, and the structural differences formation of formate, methylthiopropionate and carbon monoxide (CO) [1,3]. Subsequent research the resultthe of subtle differences metal–ligand bonddifferences lengths, which trigger the formation of secondary between two enzymes areinthe result of subtle in metal–ligand bond lengths, which showed that the same four residues bound the metal in either case, and the structural differences structural in the. The metal-dependent dual functionality of ARD has been confirmed in vitro for trigger the formation of secondary structural features in the Ni-bound form that are absent in Fe–. Breast, cervical, colon, kidney, lung, prostate, fibrosarcoma, osteogenic sarcoma, glioblastoma, neuroblastoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
