Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic glycerol-3-phosphate dehydrogenase (cG3PDH) occupies the branch point between the glycolytic pathway and triglyceride biosynthesis. However, the regulatory mechanism of the cG3PDH activity has remained obscure. Here we report that cG3PDH is efficiently inhibited by modification of the thiol group through a redox mechanism. In this study, we found that sodium selenite and nitric oxide (NO) donors such as S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine inhibited cG3PDH activity, and that similar effects could be achieved with selenium metabolites such as selenocysteine and selenomethionine. Furthermore, we found that reducing agents, such as dithiothreitol and beta-mercaptoethanol, restored the cG3PDH activity suppressed by selenite and NO both in vitro and in cultured cells. Buthionine sulfoximine depleted levels of both reduced glutathione and the oxidized form but had no effect on the suppression of cG3PDH activity by selenite in cultured cells. Moreover, thiol-reactive agents, such as N-ethylmaleimide and o-iodosobenzoic acid, blocked the enzyme activity of cG3PDH through the modification of redox-sensitive cysteine residues in cG3PDH. The inhibitor of NO synthase, L-N(G)-nitro-arginine, restored the cG3PDH activity inhibited by NO in cultured cells, whereas the inhibitor of guanylyl cyclase, 1H-[1,2,4] oxadiazole[4,3-alpha] quinoxalin-1-one (ODQ), has no effect. NO directly inhibits cG3PDH activity not via a cGMP-dependent mechanism. Finally, using site-directed mutagenesis, we found that Cys(102) of cG3PDH was sensitive to both selenite and NO. From the results, we suggest that cG3PDH is a target of cellular redox regulation.
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PMID:Redox regulation of cytosolic glycerol-3-phosphate dehydrogenase: Cys(102) is the target of the redox control and essential for the catalytic activity. 1185 59

Isatin is an endogenous indole widely distributed in mammalian tissues and body fluids. The presence of isatin-binding proteins has been recognised in particulate and soluble fractions of various organs and tissues. However, identified targets of isatin action (monoamine oxidase, natriuretic peptide receptor type A and soluble NO-stimulated guanylate cyclase) cannot account for all biological activity of this compound. Highly purified glycerol-3-phosphate dehydrogenase (GPDH) from rabbit muscle effectively interacts with the isatin analogue immobilised on the cuvette of IAsys optical biosensor. This effect was specific because the other NAD-dependent cytosolic enzyme purified from rabbit muscle, lactate dehydrogenase failed to interact with the immobilised isatin analogue. Replacement of the cuvette medium for washing buffer did not cause total dissociation of GPDH-isatin complexes. This suggests involvement of several types of enzyme-isatin interaction including tight binding. Low (10 microM) and high (100 microM) concentrations of isatin caused different effects on GPDH activity: the former significantly increased apparent Km for NAD, whereas the latter decreased apparent Vmax and increased Km.
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PMID:[Glycerol-3-phosphate dehydrogenase--cytosolic isatin-binding protein]. 1611 92