Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stereospecificity of the active center of acetylcholinesterase from human erythrocytes (AChE) and butyrylcholinesterase from horse blood serum (BuChE) in reactions with enantiomers of irreversible organophosphorus inhibitors (OPI) with asymmetrical central phosphorus atom and different structure of the leaving moiety: C2H5O(CH3)P(O)SR, where R = C2H7; C6H13: C4H4SC2H5; C2H4SC2H5 and C2H4S(CH3)C2H5, was studied. The strongest inhibiting effect with respect to cholinesterases was exerted by (-)-isomers of the OPI tested. The differences in the inhibiting activity of (-) and (+)-isomers were especially well-pronounced for OPI with R = C3H7 and C4H4SC2H5. The differences in the inhibiting activity of the enantiomers suggest that the stereospecificity of the active center of AChE was the highest and that of BuChE was considerably lower. After treatment by N,N-dimethyl-2-phenylaziridinium ions which specifically and irreversibly modify the anionic groups on the active surface of AChE, the stereospecificity of the latter is decreased and is approximated to that of BuChE. The differences in stereospecificity of AChE and BuChE are probably due to the considerable differences in the spatial structure of the enzyme active centers.
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PMID:[Stereospecificity of active centers of acylcholinesterases]. 709 83

The ultrastructural relationship between the receptor nerve fiber and the surrounding lamellae in Krause end-bulbs was discussed. Many sites of specialized junctions of symmetrical or asymmetrical type along the receptor nerve fiber and the surrounding lamellae were found. In addition, in close vicinity to them, spine-like digitations of the receptor nerve fiber, filled mainly with small clear vesicles, were observed. Mitochondrion-like cholinesterase-positive structures bulging in some cytoplasmic lamellae were also found. It is suggested that a functional link might exist between the specialized junctions, digitations and mitochrondrion-like structures in the transformation of external mechanical stimuli into nerve impulses.
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PMID:Ultrastructural relationships between the receptor nerve fiber and surrounding lamellae in Krause end-bulbs. 729 21

The study was concerned with cholinesterase activity and acetylcholine content in the cortical tissue of the human brain, obtained in autopsy and during neurosurgery. A symmetry of cholinesterase activity was found in paired cortical zones of the cutaneous analyser, while in the cortical substance of the motor analyser, its activity was asymmetrical. In the parietal cortex the acetylcholine content was almost equal on two sides; a tendency to its asymmetry was noted in the frontal area. These characteristics of interhemispheric transmitter-enzyme relations between symmetrical cortical centres seem to be a link in the mechanism underlying paired and asymmetrical activity of cortical areas of the cerebral hemispheres in humans.
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PMID:[Neurochemical asymmetry of human cerebral hemispheres]. 743 51

In patients with hyperlipaemia, serum paraoxonase activities were polymodally distributed with 75% individuals in the low activity mode. In the same patients the distribution of serum cholinesterase activities was unimodal, but asymmetrical. Patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus had slightly higher cholinesterase activities than patients with hyperlipaemia only.
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PMID:Serum paraoxonase and cholinesterase activities in individuals with lipid and glucose metabolism disorders. 839 41

The combination of antagonism at histamine H(3) receptors and inhibition of acetylcholinesterase has been recently proposed as an approach to devise putative new therapeutic agents for cognitive diseases. The 4,4'-biphenyl fragment has been reported by us as a rigid scaffold leading to potent and selective non-imidazole H(3)-antagonists. Starting from these premises, the current work presents an expanded series of histamine H(3) receptor antagonists, characterized by a central 4,4'-biphenyl scaffold, where the structure-activity profile of both mono-basic and di-basic compounds is further explored and their ability to inhibit rat brain cholinesterase activity is determined. The steric properties and basicity of the terminal groups were modulated in symmetrical compounds, carrying identical substituents, and in asymmetrical compounds, having a piperidine ring at one end and different groups at the other. The length of the linker connecting the biphenyl scaffold to the terminal groups was also modulated. Binding studies at rat and human H(3) receptors evidenced the highest binding affinities for di-basic compounds, in the order of nM concentrations, and that the steric requirements for the two terminal groups are different. Many potent compounds showed good selectivity profiles over the other histamine receptors. Interestingly, some derivatives displayed a moderate ability to inhibit rat brain cholinesterase, for example compound 12 (1-[2-(4'-piperidinomethyl-biphenyl-4-yl)ethyl]piperidine) has a pIC(50)=5.96 for cholinesterase inhibition and high H(3) receptor binding affinity and antagonist potency (pK(i)=8.70; pK(B)=9.28). These compounds can be considered as rigid analogs of a recently reported class of dual-acting compounds and as a promising starting point for the design of new H(3)-antagonists with anti-cholinesterase activity.
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PMID:Synthesis and structure-activity relationships for biphenyl H3 receptor antagonists with moderate anti-cholinesterase activity. 1897 27

Clinical indications of amyloid imaging in atypical dementia remain unclear. We report a 68-year-old female without past psychiatric history who was hospitalized for auditory hallucinations and persecutory delusions associated with cognitive and motor deficits. Although psychotic symptoms resolved with antipsychotic treatment, cognitive and motor impairments remained. She further showed severe visuoconstructive and executive deficits, ideomotor apraxia, elements of Gerstmann's syndrome, bilateral agraphesthesia and discrete asymmetric motor deficits. Blood tests were unremarkable. Structural brain imaging revealed diffuse fronto-temporo-parietal atrophy, which was most severe in the parietal regions. Meanwhile, FDG-PET suggested asymmetrical fronto-temporo-parietal hypometabolism, with sparing of the posterior cingulate gyrus. A diagnosis of possible corticobasal syndrome (CBS) was made. Amyloid-PET using the novel tracer NAV4694 was ordered, and revealed significant deposition of fibrillar amyloid (SUVR 2.05). The primary diagnosis was CBS with underlying Alzheimer pathology and treatment with a cholinesterase inhibitor was initiated. Determination of underlying pathological CBS subtype is not simple even when based on extensive investigation including clinical presentation, atrophy patterns on MRI, and regional hypometabolism on FDG-PET. By contrast, amyloid imaging quickly confirmed Alzheimer pathology, and allowed rapid initiation of treatment in this complex case with early psychiatric symptoms. This case study illustrates the clinical utility of amyloid imaging in the setting of atypical cases seen in a tertiary memory clinic.
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PMID:Clinical Utility of Amyloid Imaging in a Complex Case of Corticobasal Syndrome Presenting with Psychiatric Symptoms. 2622 55