Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Final Progress Reports: University of Arizona: The Human Genetics of Arsenic Biotransformation

Superfund Research Program

The Human Genetics of Arsenic Biotransformation

Project Leader: H. Vasken Aposhian
Grant Number: P42ES004940
Funding Period: 2000-2010

Project-Specific Links

Connect with the Grant Recipients

Visit the grantee's eNewsletter page Visit the grantee's eNewsletter page Visit the grantee's Twitter page Visit the grantee's Instagram page Visit the grantee's Video page

Final Progress Reports

Year:   2009  2004 

Over the past funding period, Dr. Aposhian’s laboratory was the first to show that mammals have an arsenate reductase, which is the same protein as purine phosphorylase. Another important finding was methylation of inorganic arsenic is not a detoxification process. Rather, it is the bioactivation of inorganic arsenite to MMAIII and DMAIII which is more toxic than inorganic arsenite and that MMAIII has been found in the urine of individuals exposed to inorganic arsenic. This finding has completely revolutionized how people investigating the toxicology and carcinogenicity of inorganic arsenic now look at and study this major environmental problem. The importance of MMAIII and DMAIII toxicity will be important in risk assessment and in understanding inorganic arsenic carcinogenicity.

Dr. Aposhian has found that human MMA(V) reductase and hGSTO1-11 are identical proteins.  This protein is a crucial enzyme in the biotransformation of inorganic arsenic.  It catalyzes the reduction of arsenate, MMA(V), and DMA(V).  MALDI-TOF and MS/MS analysis demonstrated that five molecules of GSH are bound to one subunit monomer of hGSTO1-1; four of the five cysteines were glutathionylated when GSH was present. Cys-32 in the active center, however, exists mostly in the sulfhydryl.  Understanding the mechanism of reduction of arsenic-V species to their more toxic arsenic-III forms is critical for determining how tissues (people) activate arsenic to more toxic forms.

to Top