Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells.

ABSTRACT:

Background

Loss of function of fumarate hydratase (FH), the mitochondrial tumor suppressor and tricarboxylic acid (TCA) cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate in these cells has been linked to the tumorigenic process. However, little is known about the overall effects of the loss of FH on cellular metabolism.

Methods

We performed comprehensive metabolomic analyses of urine from Fh1-deficient mice and stable isotopologue tracing from human and mouse FH-deficient cell lines to investigate the biochemical signature of the loss of FH.

Results

The metabolomics analysis revealed that the urea cycle metabolite argininosuccinate is a common metabolic biomarker of FH deficiency.

SUBMITTER: Zheng L 

PROVIDER: S-EPMC4108060 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature