Biomaterial Database

Inactivation of gamma-glutamylcysteine synthetase by SAPH-3 disulfide: role of the histaminyl moiety. 1991

N F Schor, and B Cheng, and J F Siuda

Department of Pediatrics, School of Pharmacy, University of Pittsburgh, PA 15213.

Certain disulfide analogues of cystamine were prepared and evaluated for the ability to inhibit gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in glutathione synthesis. The compound SAPH-3 disulfide (2a) was found to be the most effective inactivator of GCS reported to date. Studies of structural analogues of 2a indicate that the histamine moiety plays a significant role in enzyme inactivation. Substitution of methyl groups on the carbon atoms adjacent to both sulfur atoms of the disulfide drastically decreases inhibitory action, probably due to a steric repulsion near the sulfur atom at the enzyme active site.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008805	Mice, Inbred A	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	Mouse, Inbred A,Inbred A Mice,Inbred A Mouse
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004220	Disulfides	Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.	Disulfide
D005721	Glutamate-Cysteine Ligase	One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2.	gamma-Glutamyl-Cysteine Synthetase,Glutamylcysteine Synthetase,Glutamate Cysteine Ligase,Ligase, Glutamate-Cysteine,Synthetase, Glutamylcysteine,Synthetase, gamma-Glutamyl-Cysteine,gamma Glutamyl Cysteine Synthetase
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus