α1-Adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

Summary The effect of norepinephrine on fatty acid synthesis (³H₂O incorporation into fatty acids), on fatty acid oxidation to CO₂ and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 M), lipogenesis was lower (5.7±1.1 nmoles³H₂O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5±1.7; n=6, p<0.02). In contrast, (1-¹⁴C) palmitate conversion into total ketone bodies was increased to 10.9±1.8 nmoles/mg/30 min with norepinephrine, vs 8.5±1.6 in controls (p<0.05), and more (1-¹⁴C) palmitate was converted to¹⁴CO₂ with norepinephrine than in controls (1.48±0.10 nmoles/mg/30 min vs 1.06±0.11, p<0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the ₁-receptor blocker prazosin, but not by ₂ or -blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Effect of hypothalamic crude extract on the utilization of D-[14C]-glucose by the anterior pituitary,in vitro

Resumen Los efectos de extractos crudos de hipotalamo en la utilizacion deD-[¹⁴C]-glucosa por hipófisis anteriores fueram estudiados in vitro en condiciones identicas a aquelas en las cuales los extractos inducen la liberación de hormonas al medio de incubación. Los resultados indican que los extractos hipotalámicos aumentan la producción de¹⁴CO₂ por la hipófisis a partir de glucose y la incorporación de¹⁴C en proteinas del medio de incubación. Los extractos no modificaron la cantidad de¹⁴C glucose utilizada para sintesis de proteinas tissulares.     

Veränderungen des Glucoseabbaus in Kaninchenaorten unter dem Einfluss von Biguaniden

Summary The influence of biguanides on glucoseoxidation was studied in intima-preparations of rabbit aortae. With high doses (500 µg/ml) an inhibition of CO₂-formation predominantly from position C-1 of glucose was found. With 4 µg/ml there was no significant change of CO₂-for-mation from glucose.     

Über die Wirkung blutzuckersenkender Sulfonylharnstoffe auf das isolierte Rattenzwerchfell

Summary The action of blood sugar depressing sulfonylureas on glucose and oxygen uptake, as well as on glycogen content and formation of C¹⁴O₂ from uniformly labelled C¹⁴-glucose was investigated in rat hemidiaphragms incubated in phosphate buffer. The following results were obtained: (1) Tolbutamide and Carbutamide increased the glucose uptake. (2) Tolbutamide decreased the glycogen-content. (3) Oxygen uptake as well as formation of C¹⁴O₂ were increased by Tolbutamide. (4) The action of Tolbutamide and insuline was equal with respect to glucose uptake but different as regarding the glycogen content, oxygen uptake and CO₂-formation.It is concluded that sulfonylureas increase glucose oxidation in the rat hemidiaphragm probably without increasing insulin sensitivity. To our knowledge this mechanism of action has hitherto not been described.     

Über Struktur und Aktivität der den H2O2-Zerfall katalysierenden Cu2+-Komplexe. — VI. Differenzierung von nativer RNS und nativer DNS bzw. denaturierter DNS auf Grund der katalytischen Eigenschaften

Summary The catalysis of H₂O₂ decomposition by Cu²⁺-complexes of RNA and DNA has been investigated. It is shown that both complexes decompose H₂O₂, but only the Cu²⁺-RNA-system shows peroxidative activity too, e.g. only in this case the nucleotide bases are degraded. Thermal denaturation of DNA also leads to a Cu²⁺-complex with peroxidative activity, the latter being dependent on the degree of denaturation.

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V. Mitteilung:S. Petri, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 1778 (1966).

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12. Mitteilung überMetallionen und H ₂ O ₂; 11. Mitteilung:H. Ch. Curtius, P. Anders, R. Zell, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 2256 (1966).     

Einfluss einiger lipophiler Lösungsmittel in gasförmigem Zustand auf die CO2-fixierung durch Luzerne

Summary Vapourized organic solvents such as: diethyl ether, methylene chloride, carbon disulfide, benzene, and n-octane have an inhibiting effect on CO₂ fixation in alfalfa leaves (Medicago sativa). One exception is CS₂ which stimulates overall fixation up to 10 vol%. Beyond 10 vol% it inhibits overall CO₂ fixation like the other solvents, but stimulates the formation ofl-alanine as the major remaining fixation product. Proportionality exists between water insolubility of the organic solvents and their inhibiting effect on CO₂ fixation.     

Steigerung der14CO2-Bildung aus14C-Glukose bei der Ratte durch das orale Antidiabetikum Butylbiguanid-hydrochlorid

Summary Comparative investigations were carried out in rats to determine the effect of butylbiguanide and of insulin on the oxidation of uniform¹⁴C-labelled glucose. The administration of equally hypoglycaemic active doses of butylbiguanide (250 mg per kg orally) or of insulin (2 IU s.c.), together with 0.1 µC¹⁴C-glucose, caused similar increases in the elimination rate of¹⁴CO₂.

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Die Ergebnisse wurden auszugsweise vorgetragen anlässlich der 4. Tagung der Europäischen Gesellschaft für Diabetologie, Löwen 1968.     

Obtention d'un dérivé du sclaréol à partir de l'ambréine

Summary One of the products of the chromic acid oxidation of the animal triterpene ambreine (V) has been identified with the lactone C₁₆H₂₆O₂ (III) whichRuzicka and coll. had isolated by oxidation of the plant diterpene sclareol (II). This identification confirms recent findings of the authors and ofRuzicka, Dürst andJeger and shows that the hydroxyle of ambreine (V) is at the same place as the hydroxyle of sclareol which is attached to the perhydronaphtalene ring.

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4^me communication sur les constituants de l'ambre gris     

Wirkung der Glutaminsäure auf die experimentelle Isoniazid-Schädigung peripherer Nerven bei Ratten

Summary Glutamic acid does not, either in small or in large doses, inhibit the degeneration of the medullary sheath of peripheral nerves in rats, induced within 15 days by addition of 0.25% of isoniazid to their diet. The detoxicating effect of glutamic acid, as described byCedrangolo ¹, thus only applies to the general toxic symptoms of the acute INH-intoxication, as is the case for vitamins B₂, B₁₂, A, E, K, and niacinamide.     

Regulation ofL-valine absorption by opioids interacting withμ-receptors in rabbit ileum

In intact tissue, [d-Ala²,MePhe⁴, Gly-ol⁵] enkephalin (10^–5 M;-ligand), diminsihed short-circuit current (I_sc) and increased water, Na⁺ and Cl^– net fluxes in vitro under open circuit conditions; it also inhibitedL-valine absorption andL-valine-dependent variations of short-circuit current (I_{sc, val}). Naloxone (10^–6 M) antagonized these effects. In the absence of the muscularis and myenteric plexus this enkephalin or morphine (-ligand) reduced I_sc and I_{sc, val}. These enkephalin effects occurred at different times. Different concentrations of enkephalin were tested for their effects on I_{sc, val}. [d-Ala²,d-Leu⁵] enkephalin (mainly a -ligand) significantly decreased I_sc but not I_{sc, val}. The reduction ofL-valine absorption does not depend on the effects on basal ion transport. Interaction of opioids with-receptors located in the submucosal plexus and/or in the epithelial cell accounts for this reduction. This enkephalin effect seems to be at least partially under the control of the myenteric plexus.     

Zur Kenntnis des Muscarins

Summary The alkaloid muscarin was isolated from fly agaric. The analyses of crystallized salts (chloride, tetra-chloroaurate,Reinecke's salt) led to C₉H₂₀O₂N⁺ as the simplest formula. The presence of aldehyde and tri-methyl-ammonium groups, which had been assumed hitherto, could not be proved. The quaternary nature of the nitrogen atom was shown. Pharmacological tests on frog heart, rabbit gut and cats show the purely peripheral parasympathomimetic effect of the smallest doses.     

Dissociation-constants of metal-ion-complexes with alkaline phosphatase from pig kidney

Summary Using metal-ion buffers it was possible to remove Zn²⁺, Mg²⁺ and Mn²⁺ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are K_EMg:4·10^–7 M, K_EMn:4·10^–8 M and K_EZn:8·10^–13 M (22°C, pH:9.6, :0.07).Acknowledgement: The authors thank Dr.H. U. Wolf for helpful suggestions and valuable discussion and MissH. Köth for technical assistance.     

Incorporation of [14C] amino acids into liver S-RNA of chick. Effect of orotic acid and vitamin B12

Riassunto La somministrazione dietetica di vitamina B₁₂ e di acido orotico determina un aumento della incorporazione dellal-serina C¹⁴ nello RNA solubile del fegato di pulcino carente di B₁₂, mentre non è in grado di influenzare quella dellal-leucina¹⁴C e dellal-metionina¹⁴C.     

La voie du pentose phosphate dans le métabolisme du glucose et son interaction avec la glutathion-réductase dans les noyaux de foie de rat

Summary Rat liver nuclei, isolated in sucrose medium, convert carbon-1 of glucose-6-phosphate to CO₂ via the 6-phosphogluconic acid oxidative pathway. Conversion of glucose-1-¹⁴C to¹⁴CO₂ by the cytoplasmic fraction is greatly inhibited by nuclei. In the presence of low concentrations of NADP, the CO₂ formed by nuclei is markedly increased by the addition of GSSG.     

Nachweis von Scilliglaucosidin in den Zwiebeln vonBowiea volubilis Harvey

Summary Hellebrigenin was converted to Scilliglaucosidin-19-ol and 3-Epi-Scilliglaucosidin-19-ol. This proves the correctness of the assumption ofStoll et al. ³ that the aldehydic group of Scilliglaucosidin is in position C-10.Comparison of a reduction product of Nabogenin, a substance isolated earlier from the bulbs ofBowiea volubilis Harvey, with Scilliglaucosidin-19-ol and 3-Epi-Scilliglaucosidin-19-ol showed its identity with the first named compound. This proves that the so called Nabogenin was a mixture consisting mainly of Scilliglaucosidin.

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8. Mitteilung über die Glykoside vonBowiea vocubilis Harvey und 162. Mitteilung über Glykoside und Aglykone.

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7. Mitt.:A. Katz, Helv. chim. Acta38, 1565 (1955).

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161. Mitt.:H. Kündig-Hegedüs undO. Schindler, Helv. chim. Acta39, 904 (1956).     

Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages

Hydrogen sulfide (H₂S) plays an important role in inflammation. We showed that macrophages expressed the H₂S-forming enzyme cystathionine gamma-lyase (CSE) and produced H₂S. Lipopolysaccharide (LPS) stimulated the CSE expression and H₂S production rate. l-cysteine reduced LPS-induced nitric oxide (NO) production. CSE inhibitor blocked the inhibitory effect of l-cysteine. CSE knockdown increased, whereas CSE overexpression decreased LPS-induced NO production. Dexamethasone suppressed LPS-induced CSE expression and the H₂S production rate as well as NO production. l-arginine increased, whereas N^G-nitro-l-arginine methyl ester (l-NAME) decreased LPS-induced CSE expression and H₂S production. Dexamethasone plus l-NAME significantly decreased LPS-induced CSE expression and H₂S production compared to l-NAME. Our results suggest that macrophages are one of the H₂S producing sources. H₂S might exert anti-inflammatory effects by inhibiting NO production. Dexamethasone may directly inhibit CSE expression and H₂S production, besides the NO-dependent way. Inhibition of H₂S and NO production may be a mechanism by which glucocorticoids coordinate the balance between pro- and anti-inflammatory mediators during inflammation.     

Zur Biosynthese des Cantharidins. I

Summary In contrast to the female, the adult males ofLytta vesicatoria (Coleopt. Meloidae) produced radioactive cantharidine on injection with¹⁴C-1-acetate and¹⁴C-2-mevalonate solutions. A partial degradation of the cantharidine showed that in the acetate experiment approximately of the activity occurred at C atoms 2 + 3 whereas with mevalonate approximately of the activity was at C atoms 8 + 9 and at C atoms 10 + 11. These results show that cantharidine is not formed by a tail to tail linkage of 2 isoprene units.

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Wir danken dem Schweizerischen Nationalfonds zur Förderung der wissenschaftlichen Forschung für die Unterstützung dieser Arbeit, Herrn Dr.J. Würsch (Physikalisch-chemische Abteilung der Firma F. Hoffmann-La Roche & Co. AG, Basel) für¹⁴C-2-Mevalolacton und unserer mikroanalytischen Abteilung (LeitungH. Frohofer) für die Aktivitätsbestimmungen.     

Involvement of reactive oxygen species in the microsomal S-oxidation of thiobenzamide

Summary Superoxide dismutase, catalase and methional proved capable of inhibiting the microsomal oxidation of thiobenzamide, which is most probably catalyzed by the flavin-containing monooxygenase. This indicates that excited oxygen species (e. g.·O ₂ ^– , H₂O₂, ·OH) are involved in the catalytic cycle of this enzymatic reaction. CO, which inhibits the cytochrome P-450-dependent oxygen radical formation, had no effect on the oxidation reaction, suggesting that the source of the reactive oxygen species is not the microsomal mixed-function oxidase.     

Über Peptidsynthesen,XLIV. Synthese von Ser4-Glu(NH2)8-Oxytocin (Glumitocin)

Summary Ser⁴-Glu(NH₂)⁸-Oxytocin has been synthesized. The identity of the synthetic compound with the neurohypophysal hormone (Glumitocin) recently isolated from species of cartilaginous is demonstrated.

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Über Peptidsynthesen XLIII. Mitteilung,E. Klieger, Experientia23, 620 (1967).     

The photosynthetic energy conversion process in isolated chloroplasts

Zusammenfassung Dieser kurze Überblick über das Gebiet der Photosynthese in isolierten Chloroplasten wäre unvollständig, würde nicht die Abhängigkeit des erzielten Fortschrittes von mindestens zwei «verbesserten analytischen Methoden» betont, welcheEmil Fischers ¹ 60 Jahre zurückliegende Prophezeiung erfüllen. Zur Entdeckung der Photophosphorylierung und der Kohlenhydratsynthese durch isolierte Chloroplasten war die Einführung der Isotopen-Technik in die Biologie durchvon Hevesy ¹⁰⁷ und die Entwicklung der Papierchromatographie durchMartin undSynge ¹⁰⁸ von besonderer Bedeutung.Untersuchungen an isolierten Chloroplasten führten zu einer Auffassung der Photosynthese, die sich von der herkömmlichen Ansicht — als eines CO₂-Assimilationsprozesses — unterscheidet: Die Photosynthese scheint im wesentlichen ein Prozess zur Umwandlung der Strahlungsenergie des Sonnenlichtes in chemische Energie zu sein. Diese Umwandlung steht in engerer Beziehung zur Phosphorassimilation und zur Reduktion des Eisenproteids Ferredoxin als zur Kohlensäureassimilation. Die ersten, chemisch definierten Produkte dieser Energieumwandlungsreaktion in der Photosynthese erwiesen sich nicht als Zwischenprodukte der Kohlenstoffassimilation, sondern als ATP und reduziertes Ferredoxin.

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Based, in part, on a paper presented at the Advanced Study Institute on the Biochemistry of the Chloroplasts, Aberystwyth, Wales, U.K., August 26, 1965. — The research work from the author's laboratory reported herein has been aided by grants from the National Institutes of Health, Office of Naval Research and the Charles F. Kettering Foundation.