摘要:

AbstractThe release of homovanillic acid (HVA) and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) into CSF by the monkey spinal cord was investigated with spinal subarachnoid perfusion of 20 rhesus monkeys. The preperfusion concentration of HVA in lumbar CSF was 365 ng/ml and in cisternal CSF was 365 ng/ml, while the concentrations of MHPG were 28.3 and 40.4 ng/ml respectively. HVA originating from the spinal cord appeared in the perfusate at a rate of 2.4 and MHPG at 1.4 ng/min. Treatment with probenecid either intraperitoneally or intrathecally did not alter the rate of release into CSF of these metabolites by the spinal cord but did significantly increase the rate of appearance in the cisterna magna of HVA originating from the brain. MHPG and HVA in lumbar CSF are therefore derived in part from spinal cord metab

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06986.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractBrain homogenates from young rats were assayed for their ability to synthesize cerebrosides from radioactive UDP‐galactose or UDP‐glucose and ceramide. A comparison of galactose transfer with ceramides made from different 2‐hydroxy acids showed that the shortest one tested (C7) was by far the best acceptor, while the poorest contained 18 carbon atoms; longer fatty acids were better than CIS. Glucosyltransferase, on the other hand, showed rather little chain length specificity or discrimination against hydroxy acid ceramides.Synthetic compounds analogous in structure to ceramides were tested as inhibitors of the sugar transferases. Some were found to act as sugar acceptors themselves, particularly amides of DL‐erythro‐1‐ phenyl‐2‐amino‐1,3‐propanediol. Some amides were good inhibitors of glucosyltransferase, particularly decanoyl norephedrine, decanoyl threo‐1‐phenyl‐2‐amino‐1,3‐propanediol and decenoyl phenylalaninol. The secondary amine analogous to the first of these,N‐decyl norephedrine, was also very effective. No strong inhibitors of galactosyl transferase were found, although octanoyl D‐threo‐p‐nitrophenyla‐ minopropanediol showed promise (42% inhibition at 0.3 mM). Octanoyl phenylalaninol was nearly as good an inhibitor; the inhibition appeared only after a lag period.It is suggested that the glucosyltransferase inhibitors might he useful in therapy of Gaucher's disease, by reducing the degradative lo

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06987.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe branched‐chain 2‐oxo acids which accumulate in maple‐syrup‐urine disease inhibited the production of acetylcholine and of lipids, proteins, nucleic acids and of CO2. in sliced adult rat brains incubated with [U‐14C] glucose. Inhibition of the biosynthetic reactions was proportional to the inhibition of CO2production, even though the flux of radioactivity into the biosynthetic products was less than 2% of that to CO2.The oxo acids reduced the production of14CO2, from [U‐14C] glucose and from [2‐14C]pyruvic acid more than from [1‐14C]pyruvic acid in sliced brains. They inhibited the solubilized oxoglutarate dehydrogenase complex more than they did the solubilized pyruvate dehydrogenase complex. Valine and isoleucine, which also accumulate in maple‐syrup‐urine disease, inhibited pyruvate kinase from rat brain allosterically. Quantitative comparison of the effects of the disease metabolites on cell‐free systems with their effects on fluxes in intact cells indicated that the inhibition of oxoglutarate dehydrogenase appeared to be functionally significant. The residual activities of the other enzymes studied were adequate to support the normal flux of carbohydrates.The oxo acids were effective at concentrations within the range reported to occur in patients with maple‐syrup‐urine disease. The effects on biosyntheses including that of acetylcholine would be expected to impair brain development and function and could be important in the development of brain disease in the patients. In contrast to the results with metabolites from maple‐syrup‐urine disease, metabolites which accumulate in phenylketonuria (phenylalanine and 2‐oxo‐3‐phenylpropionic acid) did not inhibit carbohydrate utilization or the biosynthetic reactions studied, under

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06988.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractEvidence for the presence of phosphatide acylhydrolase activity (EC 3.1.1) in centrifuged homogenate supernatants and extracts of squid giant axons and centrifuged homogenate supernatants of frog sciatic nerve bundles is reported. The enzyme was assayed by measurement of the rate of deacylation of [U‐14C]phosphatidyl choline. The deacylation activity in the nerve homogenate supernatants exhibits: a pH maximum at 7.2–7.4 (25°C); a calcium ion maximum at 12–13 mM‐CaCl2(aq); a Kmvalue of 3.4 × 10−4M (25°C); and a temperature maximum at 37°C. The activation energy over the range 8–37°C is 5.7

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06989.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractYoung adult male rats were fed purified diets supplying the maintenance level of the essential amino acids or the same diet devoid of histidine. Animals were sacrificed after 2, 4, 6 and 8 weeks on these diets and olfactory bulbs, whole brains and breast muscle removed for analysis of free histidine and histidinecontaining dipeptides. There was an immediate and sharp drop in the level of carnosine in the olfactory bulb of rats on the histidine‐free diet. By 8 weeks only very small amounts of this dipeptide remained. The carnosine concentration in the olfactory bulbs of the rats receiving the maintenance level of histidine also decreased in comparison with the level maintained on the stock diet; this is believed to reflect the much reduced amount of histidine in the former as compared to the latter diet. Homocarnosine disappeared completely from whole brains of rats within 2 weeks on the histidine‐free diet. Muscle carnosine decreased in both absolute terms and relative to the controls. Anserine was lower relative to the controls, but actually increased in absolute value. Histidine deficiency may be used to study the role of carnosine in olfactory funct

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06990.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractActin levels in the soluble fraction of chick embryo brain sonicates have been quantitated by polyacrylamide gel electrophoresis. Brain actin concentrations remained constant at 8.10 ± 0.9% in developing cnibryos but dropped to 6.0 ± 0.9% in adult brain. Over 80% of the total brain protein was solubilized by the sonication procedure and actin was not detected in the remaining insoluble fractio

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06991.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract‐Eight metabolites were measured in the post‐ischemic period following either 1 or 3 h of unilateral ischemia in the gerbil cerebral cortex. The levels of ATP, P‐creatine, glucose, glycogen and GABA were essentially restored by 1 h after ischemia. In the 3 h ischemic animals. glycogen continued to increase to greater than control values aftcr 5 and 20 h of recirculation. The Icvels of glutamate were unchanged during the ischemic episode, but decreased to 60% of control at Smin and 1 h after either period of ischemia. The concentrations of cyclic AMP, which were 4‐to 5‐fold elevated during ischemia. increased an additional 6‐fold 5 min after recirculation in both groups. Arter 1 h of recovery. the levels were not different from control values. After the 1 h ischemic period, lactate levels recovered between 5 and 20 h of recirculation. In the 3 h ischemic animals. lactate concentrations were still elevated even after 20 h of recirculation. These data suggest that with the exception of lactate. recovery of metabolites is not sevcrely compromiscd by either 1 or 3 h of ischemia. Furthermore, the changes in glycogen. glutamate and cyclic AMP after recirculation suggest that the recovery process is not just a rcversal of the changes observed duri

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06992.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractIncubation of brain cell suspensions with 14 mM‐phenylalanine resulted in rapid alterations of amino acid metabolism and protein synthesis. Both thc rate of uptake and the final intracellular concentration of several radioactively‐labelled amino acids were decreased by high concentrations oi phenylalanine. By prelabelling cells with radioactive amino acids, phenylalanine was also shown to effect a rapid loss of the labelled amino acids from brain cells. Amino acid analysis after the incubation of the cells with phenylalanine indicated that several amino acids were decreased in their intracellular concentrations with effects similar to those measured with radioisotopic experiments (large neutral>small and large basic>small neutral>acidic amino acids). Although amino acid uptake and efflux were altered by the presence of 14 mwphenylalanine, little or no alteration was detected in the resulting specific activity of the intracellular amino acids. High levels of phenylalanine did not significantly altcr cellular catabolism of either alanine, lysine, leucine or isoleucine. As determined by the isolation of labcllcd aminoacyl‐tRNA from cells incubated with and without phenylalanine, there was little or no alteration in the level of this precursor for radioactive alanine and lysine. There was, however, a detectable decrease in thc labelling of aminoacyl‐tRNA for leucine and isoleucine. Only aftcr correcting for the changes of the specific activity of the precursors and thcir availability to translational events, could the effects of phenylalanine on protein synthesis be established. An inhibition of the incorporation into protein for each amino acid was approximat

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06993.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractGanglioside sialic acid was determined in the layers of human frontal association cortex and rat somatosensory cortex by microchemical methods of sampling and analysis. In both cortices the distribution per unit dry weight showed three main peaks or inflections: (1) at the junction of layers II and III; (2) in the lower part of layer III at the junction with IV; and (3) at the junction of layers V and VI. These distributions parallel the occurrence of high concentrations of dendritic and axonal plexuses and their synaptic articulations. In human cortex, the concentration of ganglioside sialic acid per unit dry weight was slightly greater, the amount per cell was twice as great. and the amount per neuron present was 2‐ to 6‐fold greater than in rat somatosensory cortex. The ganglioside sialic acid per cell was 120‐ to 200‐fold greater in human association cortex than in rat retina, which is a CNS region with sparse neuropil. The results support the validity of ganglioside sialic acid as an index of the relative mass of neuronal plasma membranes in neural tissues and its usefulness in chemoanatomic quantitation of axodendritic interrelationships established by synaptic contacts with local and distant

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06994.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe cellular compartments of ciliary ganglia take up choline by a single, saturable process with Km=7.1 × 10−5M and Vmax= 4.66 pmol/min per ganglion: Denervation of the ganglia and the resultant degeneration of nerve terminals caused no significant decrease of the rate of accumulation of choline by the ganglia. This indicates that the measured uptake is by the postganglionic ncurons and nonneural elements (NNE: glial and connective tissue cells) in the ganglia. This uptakc is not dependent on metabolic energy and is not affectcd by lowcring Na+or raising K+concentrations in the incubating mcdia but is depressed in the presence of ouabain and hemicholinium‐3. The presence or Na+‐dependent. rapidly saturable uptake in the preganglionic nerve terminals which is not detectablc kinetically is, however, inferred from a decrease in ACh synthesis in dcncrvatcd prcparations and a similar decrcasc in intact ganglia incubated in low Na+ so

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb06995.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY