[Preliminary studies on inhibitors of apo-tyrosine transaminase].
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Biomedical subjects
Publications and source records attributed to C Turano.
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1. Acetylation of aspartate aminotransferase from pig heart inhibits completely the enzymic activity when the coenzyme is in the amino form (pyridoxamine phosphate) or when the coenzyme has been removed, but not when the coenzyme is in the aldehyde form (pyridoxal phosphate). 2. The group the acylation of which is responsible for the inhibition has been identified with the in-amino group of a lysine residue at the coenzyme-binding site. Moreover, in the pyridoxamine-enzyme the amino group of the coenzyme is also acetylated. 3. The reactivity of the coenzyme-binding lysine residue is greatly different in the pyridoxamine-enzyme and in the apoenzyme, suggesting the possibility of an interaction of its in-amino group with pyridoxamine or with other groups on the protein.
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A convenient method for the purification of aspartate aminotransferase [L-aspartate-2-oxoglutarate aminotransferase (EC 2.6.1.1)] from wheat germ is described. An overall purification of 150 fold was achieved. On polyacrylamide gel electrophoresis at pH 8.9 the purified enzyme revealed two protein bands both provided with enzymatic activity. The holoenzyme is readily resolved on conversion to the aminic form and gel-filtration. The apoenzyme is reactivated by pyridoxal-5-phosphate. Kinetic data indicate that a Ping-Pong mechanism is operative similar to that found for the tyrosine aminotransferase by Litwack and Cleland (1968). Phosphate ion behaves as a competitive inhibitor towards the coenzyme. The relatively low affinity between coenzyme and apoenzyme from wheat germ allowed the determination of the dissociation constants for coenzymes (pyridoxal-5'-phosphate and pyridoxamine-5'-phosphate) and of the inhibition constant for phosphate.
Glycoproteins recognized by Ulex europaeus lectin I, specific for fucose residues, have been identified in chromatin prepared from pig liver, heart and kidney nuclei. They are present among the proteins dissociated from DNA with salt solutions and, in higher amount, among the proteins dissociated with urea and guanidine. In any case these fucose-containing glycoproteins appear to have a marked tissue specificity, which suggests that they have specific regulatory roles in the processes taking place in the nuclei.
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The Authors present one case of choroid plexus papilloma localized in the third ventricle. This is in fact the only case in a series of about 4,000 patients operated on for brain tumors at the Neurosurgical Institute of the University of Rome. They consider 56 cases reported in the literature. Out of these, 43 are described and summarized in a table according to the clinical, radiological and surgical features. Twentyfive were the patients operated on, the average mortality in the cases which underwent indirect or not specified operation was 80%; that of patients submitted to a direct approach or to subtotal excision was 50%; and finally 3 patients out 13 (about 23%) who had total resection, died after surgery.
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Sustained epileptic seizures were induced in cats by means of penicillin (PCN). After a three hour period tissue from the archicortex was removed, frozen, and extracted for metabolic studies. The concentration of ATP, ADP, AMP, phosphocreatine, glucose, glucose-6-phosphate, pyruvate, lactate, glutamate and aspartate were determined. There was a 50% decrease in phosphocreatine concentration, a slight decrease in the level of ATP and a slight increase in the levels of ADP and AMP. There was a decrease in the total adenine nucleotide and the ATP/ADP and ATP/AMP ratios. The absence of a significant change in adenylate energy charge potential reflects the remarkable ability of the brain to stabilize its energy state even after intense seizure activity. A reflection of increased glycolysis is the presence of decreased glucose (nearly 50%), and increased lactate, concentrations. The metabolic changes observed in the archicortex are comparable to those observed by others in the neocortex, indicating perhaps the relative metabolic uniformity of these two types of cortex.
The present communication was part of a larger study in which penicillin induced epileptogenic activity in the hippocampus of the "cerveau isolé cat" was investigated. The discharge contralateral to the side of the PCN focus, i.e., the mirror focus, was dependent upon the integrity of the commissural pathways. Interhippocampal latencies of bisynchronous epileptogenic discharge varied between 0 and 50 msec (mean 20). Interestingly the discharges could occur absolutely simultaneously and even more surprising, the mirror focus discharge occasionally led that in the primary focus! An interpretation as to how this might occur is given.