摘要:

Abstract—Investigations of the respective effects of dietary vitamin B6deficiency and 4‐deoxypyridoxine (a vitamin B6antagonist) on GABA metabolism in rat brain have been carried out. No convulsions were observed in rats subjected to either treatment. GABA levels were lowered by both treatments, the greatest diminutions being found with the dietary deficiency. Glutamic acid decarboxylase activity was reduced under both conditions, but the loss of activity in the B6deficiency experiments could be attributed to cofactor depletion, whereas in the deoxypyridoxine experiments the loss of activity appears to be due to lower levels of available apoenzyme. The activity of GABA‐transaminase was not affected by deoxypyridoxine treatment and only moderately reduced in the B.5 deficient an

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01374.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Mice were infused intravenously for varying periods of time with L‐[U‐14C]‐ tyrosine. The specific activity of free tyrosine in the blood and the brain, and of protein‐bound tyrosine in the brain, was measured and the mean rate of protein synthesis calculated. The half‐life of mixed brain proteins was found to be close to 4 days with infusions lasting 0.5–2 h.The origin of the intracellular tyrosine pool was investigated and it was shown that 60 per cent of this was derived directly from the plasma tyrosine and 40 per cent from protein breakdown with

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01375.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The metabolic properties of synaptosome beds (deposits positioned between nylon gauzes) were studied. They respired, glycolysed, produced ATP and phosphocreatine, and metabolized [U‐14C]glucose to glutamate, aspartate, alanine and GABA at similar rates to synaptosome suspensions. Metabolic inhibitors caused massive loss of amino acids from the beds. Synaptosome beds also responded metabolically to electrical pulses; respiration and lactate production increasing by 40 per cent. Differential release of glutamate, aspartate and GABA occurred during electrical stimulation, maximum release being after 10–15 min of stimulation. This differential release also occurred when medium potassium was increased. Omitting and chelating calcium reduced or abolished this response with both forms of stimulation. Including amino acid analogues (β‐aminobutyric acid, α, γ‐diaminobutyric acid andN‐acetyl glutamic acid) in the incubation medium changed the patterns of amino acids present in the medium, indicating that under normal conditions active amino acid uptake processes are occurring in synaptosomes. Tetrodotoxin and ouabain also interfered with amino acid release without greatly affecting the response to stimulation. Cerebral cortex slices incubated between gauzes also showed a glycolytic response to electrical stimulation. GABA was the only amino acid showing a significant increase in the amount released with both potassium and electrical stimulation

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01376.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The incorporationin vivoof [3H]leucine into protein from subcellular fractions was determined in rats chronically ingesting 15 per cent ethanol for 8 months. Mitochondrial, microsomal and cell sap fractions from cerebellum, cortex cerebri and liver were investigated. The results showed a minor over‐all depression of protein synthesis in cerebellum and cortex cerebri and a slight stimulation of the incorporation of leucine into protein from liver subcellular fractions. If the animals were abstinent 24 h before injection of the isotope, the incorporation of labelled amino acids into protein was markedly increased in cerebellum and cerebral cortex but not in li

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01377.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Metabolic relationships between the four major brain gangliosides, GM1, GD1a, GDlb and GT1 were studiedin vivo. Labelled acetate and glucosamine were injected intracerebrally into 6–12‐day‐old rats and the radioactivities of the cerebral gangliosides were analysed. Radioactivity from [3H]acetate was determined in sialic acid, sphingosine and stearic acid and from [1‐14C]glucosamine in hexosamine and sialic acid. The gangliosides were labelled in proportion to their pool size. In 6 day‐old rats the labelling was approx. 30 per cent lower in the sialidase‐stable sialyl group than in the labile one. When the brain gangliosides were labelled in 12‐day‐old rats, however, the specific activities of sialidase‐labile and stable sialyl groups were the same at 0.5 months after the injection of precursors and disappeared at the same rate. The results indicate that at the age of 6 days a small pool of monosialogangliosides exists, which is converted to di‐ and trisialogangliosides. The degradation of gangliosides was studied by following the radioactivities in sphingosine and stearic acid from 2 to 6 months after the injection of labelled acetate. The specific activities of sphingosine and stearic acid decreased simultaneously at the same rate in all the four major gangliosides. The specific activity of stearic acid was the same in total brain lipids as in gangliosides. The half‐lives for the degradation of the gangliosides were age‐dependent and estimated to 60 days in adult rats. They were much shorter in younger rats but no reliable fi

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01378.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Rabbits were given an intraocular injection of [3H]acetate and [1‐14C]glucosamine. The two precursors were incorporated into the gangliosides, whose activities were measured in the retina, optic nerve, optic tract and lateral geniculate body. The radioactivities of cerebrosides and ethanolamine and choline phosphoglycerides were also determined. Gangliosides were labelled in all parts of the optic pathway, from both acetate and glucosamine. The precursors seemed to be distributed along the entire pathway shortly after injection. They were not transported with the blood and no ganglioside transport could be sh

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01379.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—Preparations of guinea pig brain nuclei, obtained by discontinuous gradient centrifugation in sucrose solutions of pH 6.7–6.8, containing 3 mM‐MgCl2and phosphate exhibited steady and reproducible oxygen uptake. Oxygen uptake was stimulated 60–70 per cent by glucose, pyruvate, oxalacetate or α‐ketoglutarate and 267 per cent by succinate. This respiratory activity was unaffected by the relative sodium or potassium ion content of the medium and by variations in the concentration of inorganic phosphate. Agents known to inhibit citric acid cycle oxidation, oxidative phosphorylation and glycolysis diminished oxygen uptake, but antibiotics inhibiting nucleic acid or protein synthesis did not. Treatment of the nuclear preparation with DNase decreased respiratory capacity, which was partially restored by the addition of polyac

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01380.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The velocity of the reaction catalysed by acyl‐CoA:l‐giycerol‐3‐phosphate acyltransferase (EC 2.3.1.15) of microsomes from rat brain was affected by the nature of the buffering agent, the ionic strength and the sucrose concentration of the reaction medium. The enzyme was inhibited by buffers based on trimethyl‐pyridine, diethyl barbituric acid, and boric acid. Buffers based on N‐ethyl morpholine, potassium phosphate, sodium arsenate, imidazole, tris and triethanolamine were not inhibitory. Dithiothreitol protected the enzyme and produced maximal activity at levels in the reaction medium between 0.2 and 2.8 mM.Optimum ionic strength was determined by varying the concentration of a potassium phosphate buffer and in this medium the optimum ionic strength was about 0.2 M. In other studies with sodium formate, potassium acetate and other salts there was a broad plateau of activity in a range about 0.2 M. A study of pH vs. activity with two different buffering agents at constant ionic strength showed a broad maximum of activity from pH 7.2 to pH 7.8. The velocity of the reaction could be further increased by the inclusion of 0.25 M‐sucrose in the reaction medium in the presence of 0.2 M salts. The sucrose effect produced maximum velocities at sucrose concentrations ranging from 0.2 to 0.6 M. The studies reported here indicate that the activity of the enzyme is dependent upon the state of hydration of the microsomal membranes and in part on the ability of the enzyme or membrane to cope with large micelles of

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01381.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—This combined histochemical and biochemical study has shown that acid proteinase activity (PH 3.5) is increased around histologically‐defined active plaques of multiple sclerosis (MS). Biochemical estimation showed that the enzyme is more active in most samples of ‘normal’ white matter in MS than in controls. A gradient of enzyme activity was observed: control white matter‐white matter distant from plaqueclose white matter‐edgsplaque. Both electrophoretic and histochemical techniques revealed a reduction or absence of basic (encephalitogenic) protein in the plaques. Electrophoresis showed a diminution of encephalitogenic protein outside some plaques. Phospholipids that remain on the base‐line of thin‐layer chromatoplates were shown to be predominantly phosphoinositides combined with encephal

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01382.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY

摘要:

Abstract—The swelling of intact, exposed primate cerebral cortex perfused in vioo under, isosmotic conditions was a linear function of the concentration of K+in perfusate over the range 25–117 mM. The K+‐dependent swelling was manifested throughout the depth of the cerebral cortex studied and was associated with an increased content of chloride in the swollen tissue, despite the constancy of the concentration of external chloride. The swelling of the cerebral cortex was a linear function of the temperature of the perfusate over the range 15–38°C, despite the constancy of the concentration of external K+. Moreover, the content of chloride in the swollen cerebral cortex was a linear function of the temperature of the overlying perfusate, despite the constancy of the external concentration of chloride. The changes in the contents of Na+and K+in the swollen cerebral cortex perfused with solutions containing constant concentrations of external Na+and K+but differing in temperature suggested that the fluid of swelling in the tissue was rich in both K+and CI‐, as had been shown previously in vitro. Perfusion of the exposed, intact cerebral cortex in uiuo with K+‐rich fluids usually involved the reciprocal reduction of the concentrations of Na+ in the perfusate to maintain isotonicity. When comparable reductions in the concentration of external Na+were achieved by replacement with choline (instead of K+), swelling of the perfused, exposed cortex was significantly less than that attributed to isotonic, K+‐rich but Na+‐poor fluids. These observations suggested that it was the elevated levels of K+rather than lowered concentrations of Na+ that promoted the swelling of the perfused cerebral cortex.The apparent rate of influx of36Cl from the perfusate into the underlying exposed and intact monkey cerebral cortex in vivo was a linear function of the concentration of K+in perfusate over the range 25–117 mM and conformed to Michaelis‐Menten kinetics when plotted according to Lineweaver and Burk. Moreover, the apparent influx of chloride from perfusate into swollen cerebral cortex was a linear function of the percentage swelling of cerebral cortex over the range 6–30 per cent. However, the apparent rate of influx of chloride from perfusate into unswollen cortex was not consistent with the linear correlation already described for swollen cerebral cortex. One reason for this discrepancy was the reduction in the size of the true (inulin) extracellular space associated with the K+‐dependent swelling of cerebral cortex in vivo. The anatomical locus for this K+‐dependent swelling of cerebral cortex was an expanded glial compartment, as demonstrated by electron‐microscopy. The parenteral administration (50 mg/kg) or local perfusion (5 mM) of acetazolamide inhibited the K+‐dependent swelling of cerebral cortex in vivo. Moreover, administration of acetazolamide inhibited the K+‐dependent increase in content of C1‐ and the K+‐dependent rate of influx of36Cl into swollen cerebral cortex. We have discussed the possible enzymatic basis of these K+‐dependent alterations in content of fluid and chloride and transport of chlorid

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1972.tb01383.x

出版商:Blackwell Publishing Ltd    

年代:1972

数据来源: WILEY