Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogen sulfide (H(2)S) is produced endogenously from l-cysteine in mammalian tissues, and may function as a neuromodulator in the brain as well as a tone regulator in smooth muscle. H(2)S is present at relatively high levels in the brain, and cystathionine beta-synthase (CBS), which is highly expressed in the hippocampus, is involved in the production of brain H(2)S. Physiological concentrations of H(2)S selectively enhance NMDA receptor-mediated currents and facilitate the induction of hippocampal long-term potentiation (LTP). The NMDA receptor subunits are directly phosphorylated at specific sites by protein kinase A (PKA), resulting in the activation of NMDA-receptor-mediated excitatory postsynaptic currents. PKA activation is also observed in the induction of LTP. Here we show that physiological concentrations of H(2)S increase the production of cAMP in primary cultures of brain cells, neuronal and glial cell lines, and Xenopus oocytes. NMDA receptors expressed on Xenopus oocyte membrane are modulated by H(2)S. This modulation by H(2)S is specifically inhibited by adenylyl cyclase-specific inhibitor MDL-12, 330A. The present findings provide a mechanism for the previous observation that H(2)S modulates NMDA receptors and enhances the induction of LTP.
 ...
PMID:Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. 1062 86

Cystathionine beta-synthase (CBS; EC 4.2.1.22) is a key enzyme in the generation of cysteine from methionine. A deficiency of CBS leads to homocystinuria, an inherited human disease characterized by mental retardation, seizures, psychiatric disturbances, skeletal abnormalities, and vascular disorders; however, the underlying mechanisms remain largely unknown. Here, we show the regional and cellular distribution of CBS in the adult and developing mouse brain. In the adult mouse brain, CBS was expressed ubiquitously, but it is expressed most intensely in the cerebellar molecular layer and hippocampal dentate gyrus. Immunohistochemical analysis revealed that CBS is preferentially expressed in cerebellar Bergmann glia and in astrocytes throughout the brain. At early developmental stages, CBS was expressed in neuroepithelial cells in the ventricular zone, but its expression changed to radial glial cells and then to astrocytes during the late embryonic and neonatal periods. CBS was most highly expressed in juvenile brain, and a striking induction was observed in cultured astrocytes in response to EGF, TGF-alpha, cAMP, and dexamethasone. Moreover, CBS was significantly accumulated in reactive astrocytes in the hippocampus after kainic acid-induced seizures, and cerebellar morphological abnormalities were observed in CBS-deficient mice. Taken together, these results suggest that CBS plays a crucial role in the development and maintenance of the CNS and that radial glia/astrocyte dysfunction might be involved in the complex neuropathological features associated with abnormal homocysteine metabolism.
 ...
PMID:Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. 1616 63

Current evidence suggests that hydrogen sulfide (H2S) plays an important role in brain functions, probably acting as a neuromodulator as well as an intracellular messenger. In the mammalian CNS, H2S is formed from the amino acid cysteine by the action of cystathionine beta-synthase (CBS) with serine (Ser) as the by-product. As CBS is a calcium and calmodulin dependent enzyme, the biosynthesis of H2S should be acutely controlled by the intracellular concentration of calcium. In addition, it is also regulated by S-adenosylmethionine which acts as an allosteric activator of CBS. H2S, as a sulfhydryl compound, has similar reducing properties as glutathione. In neurons, H2S stimulates the production of cAMP probably by direct activation of adenylyl cyclase and thus activate cAMP-dependent processes. In astrocytes, H2S increases intracellular calcium to an extent capable of inducing and propagating a "calcium wave", which is a form of calcium signaling among these cells. Possible physiological functions of H2S include potentiating long-term potentials through activation of the NMDA receptors, regulating the redox status, maintaining the excitatory/inhibitory balance in neurotransmission, and inhibiting oxidative damage through scavenging free radicals and reactive species. H2S is also involved in CNS pathologies such as stroke and Alzheimer's disease. In stroke, H2S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.
 ...
PMID:Hydrogen sulfide: neurochemistry and neurobiology. 1762 56

The purpose of the present study was to verify our assumption that rhythmic respiratory activity may be regulated by endogenous hydrogen sulfide (H(2)S) in the medullary slices of neonatal rats. We found that a moderate concentration of donor of H(2)S, NaHS, mainly induced diphasic respiratory responses indicated by changes of discharge frequency (DF) of hypoglossal rootlets, an initial inhibitory stage followed by a later excitatory one. Cystathionine beta-synthase (CBS) substrate, cysteine (CYS), exerted similar effects. CBS inhibitor, NH(2)OH, could eliminate both inhibitory and excitatory effects in the two stages induced by CYS. K(ATP) channel blocker, glibenclamide (Gl), could eliminate the decrease in DF in the initial stage, but not the increase in the later one. On the other hand, adenyl cyclase (AC) inhibitor, SQ-22536 (SQ) could eliminate the increase in DF in the later stage, but not the decrease in the initial one, of the rootlets caused by NaHS. Co-application of Gl and SQ eliminated both inhibitory and excitatory effect induced by NaHS. The cAMP level was increased in the later stage but not in the initial one by NaHS, and the increase in the cAMP level could be eliminated by SQ. It can be concluded that the endogenous H(2)S could be produced through the CBS-H(2)S pathway and could be involved in the control of the central rhythmic respiration in the in vitro medullary slices of neonatal rats by opening K(ATP) channels and activating AC-cAMP pathway of the neurons.
 ...
PMID:Endogenous hydrogen sulfide is involved in regulation of respiration in medullary slice of neonatal rats. 1879