Cysteinesulfinate decarboxylase: Characterization, inhibition, and metabolic role in taurine formation
Cysteinesulfinate decarboxylase, an enzyme that plays a major role in the formation of taurine from cysteine, has been purified from rat liver to homogeneity and characterized. The physical properties of the enzyme were studied, along with its substrate specificity. Multiple forms of the enzyme were found in rat liver, kidney, and brain with isoelectric points ranging from pH 5.6 to 4.9. These multiple forms did not differ in their substrate specificity. It was found by using gel electrofocusing and polyclonal antibodies raised to the liver enzyme that the different forms of cysteinesulfinate decarboxylase are identical in the various rat tissues studied. Various inhibitors of the enzyme were tested both in vitro and in vivo in order to evaluate the role of cysteinesulfinate decarboxylase in taurine formation in mammalian tissues. In in vitro studies, cysteinesulfinate decarboxylase was irreversibly inhibited by {beta}-ethylidene-DL-aspartate (Ki = 10 mM), and competitive inhibition was found using mercaptomethylsuccinate (Ki = 0.1 mM) and D-cysteinesulfinate (Ki = 0.32 mM) when L-cysteinesulfinate was used as a substrate. In order to be able to test these inhibitors in vivo, L-(1-{sup 14}C)cysteinesulfonate was evaluated as a probe for the in vivo measurement of cysteinesulfinate decarboxylase activity. The metabolism of cysteinesulfonate and the product of its transamination, {beta}-sulfopyruvate, was studied, and it was found that L-(1-{sup 14}C)cysteinesulfonate is an accurate and convenient probe for cysteinesulfinate decarboxylase activity. Using L-(1-{sup 14}C)cysteinesulfonate, it was found that D-cysteinesulfinate inhibits cysteinesulfinate decarboxylase activity by greater than 90% in the intact mouse and that inhibition lasts for up to fifteen hours.
- Research Organization:
- Cornell Univ., New York, NY (United States). Medical Coll.
- OSTI ID:
- 5673837
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CYSTEINE
METABOLISM
DECARBOXYLASES
CHEMICAL COMPOSITION
TAURINE
BIOSYNTHESIS
BIOLOGICAL FUNCTIONS
CARBON 14 COMPOUNDS
ENZYME INHIBITORS
LIVER
PHYSICAL PROPERTIES
RATS
TRACER TECHNIQUES
AMINES
AMINO ACIDS
ANIMALS
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYASES
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RODENTS
SULFONIC ACIDS
SYNTHESIS
THIOLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
550501 - Metabolism- Tracer Techniques