J. Biol. Chem., Vol. 263, Issue 33, 17262-17269, 11, 1988
Persulfide generated from L-cysteine inactivates tyrosine aminotransferase. Requirement for a protein with cysteine oxidase activity and gamma-cystathionase
JL Hargrove
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.
Liver cytosols contain factors that produce an inhibitor of tyrosine
aminotransferase and other enzymes when incubated with L-cysteine or L-
cystine. Cystine-dependent inactivation was caused by cystathionase and
required pyridoxal 5'-phosphate, but a second protein was needed to
reconstitute cysteine-dependent inactivation. A cytosolic protein was
isolated that oxidized free cysteine and brought about inactivation of
tyrosine aminotransferase when coincubated with cystathionase. Hematin also
oxidized cysteine, which led to cysteine-dependent inactivation of tyrosine
aminotransferase in the presence of cystathionase. The inactivation of
tyrosine aminotransferase involved three steps: initial oxidation of
cysteine to form cystine; desulfuration of cystine catalyzed by
cystathionase to form the persulfide, thiocysteine; and reaction of
thiocysteine (or products of its decomposition) with proteins to form
protein-bound sulfane. Since dithiothreitol reactivated tyrosine
aminotransferase, the sulfane probably inactivated the enzyme by oxidation
of thiol groups. The present results do not indicate whether the cysteine
oxidase activity is enzymatic nor do they prove which form of polysulfide
inactivates tyrosine aminotransferase. Reduced glutathione greatly slowed
the rates at which sulfane accumulated and at which tyrosine
aminotransferase was inactivated. Incubation of DL-cystathionine with liver
cytosols led to formation of cysteine, which was oxidized and cleaved to
form persulfide, and caused inactivation of tyrosine aminotransferase.
Thus, sulfane sulfur that is generated by an enzyme of the transulfuration
pathway inactivates a transaminase by nonselective oxidation of
enzyme-bound thiol groups.
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