Cysteinesulfinate decarboxylase: Characterization, inhibition, and metabolic role in taurine formation
Thesis/Dissertation
·
OSTI ID:5673837
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
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
550501 -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
CHEMICAL COMPOSITION
CYSTEINE
DECARBOXYLASES
DIGESTIVE SYSTEM
ENZYME INHIBITORS
ENZYMES
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LYASES
MAMMALS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHYSICAL PROPERTIES
RATS
RODENTS
SULFONIC ACIDS
SYNTHESIS
TAURINE
THIOLS
TRACER TECHNIQUES
VERTEBRATES
550501 -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
CHEMICAL COMPOSITION
CYSTEINE
DECARBOXYLASES
DIGESTIVE SYSTEM
ENZYME INHIBITORS
ENZYMES
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LYASES
MAMMALS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHYSICAL PROPERTIES
RATS
RODENTS
SULFONIC ACIDS
SYNTHESIS
TAURINE
THIOLS
TRACER TECHNIQUES
VERTEBRATES