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Human Acireductone Dioxygenase (HsARD), Cancer and Human Health: Black Hat, White Hat or Gray?

1
Department of Chemistry, Brandeis University, Waltham, MA 02454, USA
2
Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
*
Author to whom correspondence should be addressed.
Inorganics 2019, 7(8), 101; https://doi.org/10.3390/inorganics7080101
Received: 21 June 2019 / Revised: 2 August 2019 / Accepted: 14 August 2019 / Published: 18 August 2019
(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)
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. View Full-Text
Keywords: AD11; nickel-dependent enzyme; methionine salvage pathway; methionine; S-adenosylmethionine (SAM); methylthioadenosine (MTA); enolase phosphatase 1 (ENOPH1); polyamine; matrix metalloproteinase MT1 (MT1-MMP) AD11; nickel-dependent enzyme; methionine salvage pathway; methionine; S-adenosylmethionine (SAM); methylthioadenosine (MTA); enolase phosphatase 1 (ENOPH1); polyamine; matrix metalloproteinase MT1 (MT1-MMP)
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Liu, X.; Pochapsky, T.C. Human Acireductone Dioxygenase (HsARD), Cancer and Human Health: Black Hat, White Hat or Gray? Inorganics 2019, 7, 101.

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