Unified gas chromatographic-mass spectrometric method for quantitating tyrosine metabolites in urine and plasma.

Tyrosine and many of its catabolites play significant roles in the in the toxicity associated with acquired and congenital forms of hypertyrosinemia. We now report a specific and sensitive GC/MS method for the simultaneous determination of tyrosine metabolites maleylacetone (MA), fumarylacetone (FA), succinylacetone (SA), fumarate and acetoacetate in urine and plasma. Tyrosine metabolites and an internal standard, 2-oxohexanoic acid (OHA), in urine or plasma samples were derivatized to their methyl esters with a 12% boron trifluoride-methanol complex (12%BF3-MeOH).

Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases levels of toxic tyrosine catabolites in rodents.

Dichloroacetate (DCA) is both an environmental contaminant and an investigational drug for diseases involving perturbed mitochondrial energetics. DCA is biotransformed to glyoxylate by maleylacetoacetate isomerase (MAAI). Previous studies have shown that DCA decreases MAAI activity in rat liver in a time- and dose-dependent manner and may target the protein for degradation in vivo.