The oxidative metabolism ofα-chlorohydrin and the chemical induction of spermatocoeles

Summary -Chlorohydrin (I) is oxidatively metabolized to -chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.     

Eine neue Umlagerungsreaktion und ein neues Prinzip zum Aufbau von Peptidketten

Summary In a series of model reactions, it is shown that residues of-aminoacids may be inserted by a particular rearrangement into certain carboxyl or carbonylamido groups. Repeated insertion results in the formation of a peptide derivative. It is concluded that natural peptides or proteins must not necessarily be formed by head to tail combination of aminoacids. Other implications of the new principle are discussed.

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Vorgetragen am XIV. Internationalen Kongress für Reine und Angewandte Chemie, 21. bis 27. Juli 1955, Zürich.     

Chelate aus Diarylborinsäuren undβ-Ketosäureestern

Summary Diarylborinic acids form stable chelates with-keto acid esters. Borinic acids, when being synthetized, can be stabilized in compounds resulting from the combination with-keto acid esters. The chelates so formed are suitable—like the free borinic acids or their anhydrides—for further transformation. These chelates have several advantages in comparison with those formed with-amino ethanol.     

ω10-Lipoxygenase products of α-linolenic acid are esterified to phospholipids inHydra vulgaris

We have recently reported the occurrence of 9(R)-hydroxy-, 9(R)-hydroperoxy- and 9-keto-octadeca-10E,12Z,15Z-trienoic acids (9-HOTrE, 9-HPOTrE and 9-KOTrE) inHydra vulgaris, and their biosynthesis from -linolenic acid (-LA) through the action of an enantioselective 10(R)-lipoxygenase (10-LO). Here we describe the finding of these -LA metabolites as esters to the 2-position of phosphatidylcholine, phosphatidylethanolamine and, in trace amounts, phosphatidylinositol. Small amounts of a compound co-eluting with an authentic standard of 9(R)-hydroxy-octadeca-10E,12Z-dienoic acid, a metabolite potentially derived from the action of 10-LO on linoleic acid, were also found esterified with phospholipids. Since direct peroxidation of membrane lipids has been described, experiments were aimed at establishing whether -LA metabolite-containing phospholipids could originate, inH. vulgaris, from either spontaneous or 10-LO-catalyzed oxidation of phospholipid-bound -LA. Incubation of either unlabelled or radiolabelled PUFA-containing phosphoglycerides withH. vulgaris 10-LO did not result in their peroxidation. This suggests that -LA and LA metabolites are incorporated into glycerophospholipids after their formation by 10-LO, and that, as in mamals, membrane phospholipids may serve as a reservoir for these bioactive compounds. This is the first example in an invertebrate species of lipoxygenase products esterified to phosphoglycerides.     

Single amino acid substitutions insn-glycerol-3-phosphate dehydrogenase allozymes fromDrosophila virilis

Summary The amino acid sequence was compared among the three allelic variants (allozymes) ofsn-glycerol-3-phosphate dehydrogenase inD. virilis, which are detected by one-dimensional electrophoresis. The GPDH^f variant was different from the GPDH^m by only one substitution of 68-lysine for asparagine; GPDH^s differed from GPDH^m by substitution of 127-glycine for arginine. No electrophoretically silent substitutions were found in a total of 352 amino acid residues.     

Unusual antimicrobial compounds fromAeollanthus buchnerianus

Using bioassay guided isolation, three novel 12 carbon polyoxygenated fatty acids and a novel abietane diterpene have been isolated from the the chloroform extract of aerial parts ofAeollanthus buchnerianus (Lamiaceae). Rigorous spectroscopic methods were used for compound identification. (Z,Z)-8-acetoxy-5-hydroxydodeca-2,6-dienoic acid and (Z,Z)-5,8-dihydroxydodeca-2,6-dienoic acid inhibited the spore germination ofCladosporium cucumerinum (both with Minimum Inhibitory Dose (MID) values of 1 g) andAspergillus niger (MID 5 and 25 g respectively). Further, they also reduced the hyphal growth ofPythium ultimum. (Z)-5-hydroxy-6,7,8-triacetoxydodeca-2-dienoic acid exhibited short term inhibition of the growth ofCladosporium cucumerinum. The novel abietane diterpenoid, (rel)-14-acetoxyabiet-7-en-18-oic acid inhibited the growth of the gram positive bacteriaBacillus subtilis, staphylococcus aureus andStreptomyces scabies (MIC values 80, 20 and 20 g ml^–1 respectively).     

Hydra vulgaris ω10-lipoxygenase is used in vivo to synthesize new α-linolenic acid metabolites

Previous studies conducted in cytosolic extracts of the freshwater hydrozoanHydra vulgaris led to the finding of an abundant 11(R)-lipoxygenase catalyzing the peroxidation of polyunsaturated fatty acid (PUFAs) on the tenth carbon atom from the aliphatic end (10 peroxidation). Here we describe experiments aimed at identifying the actual metabolites generated in vivo by such enzymic activity. Homogenates ofH. vulgaris polyps were analyzed by HPLC. This showed the presence of three major components chromatographically identical to three metabolites obtained when incubating the homogenates with exogenous -linolenic acid (-LA). The presence, in extracts of polyps prelabelled with [¹⁴C]--linolenic acid, of radioactive metabolites displaying the same chromatographic properties, substantiated the hypothesis that the natural products isolated in vivo are derived from -LA. Gas chromatographic analyses revealed that this was the most abundant PUFA in both free and phosphoglyceride-bound fatty acid pools. [¹H]-NMR analysis of the endogenous substances, carried out in comparison with products obtained from exogenously incubated -LA, indicated that their structures were those of 9-hydroxy-, 9-hydroperoxy- and 9-keto-octadeca-10E-12Z-15Z-trienoic acids (9--HOTrE,-HPOTrE and-KOTrE).Hydra homogenates transformed 9--HPOTrE partly into 9--HOTrE and partly into 9--KOTrE. Chiral phase HPLC conducted on 9--HOTrE established that this metabolite was composed mostly of theR anantiomer. These observations, and the finding that the presence of exogenous arachidonic acid in incubated homogenates significantly reduces the production of -LA metabolites, provide strong evidence that these compounds are produced by an enzymic activity identical to the previously-describedH. vulgaris (R)-10-lipoxygenase. Further experiments suggested that -LA, acting as the native substrate for this enzyme, is mainly esterified on the 2 position ofHydra phosphoglycerides, and that the production of the -LA metabolites described here for the first time from natural sources, can be potentially enhanced in vivo by stimuli activating phospholipase A₂.     

Kelletinin I and kelletinin A from the marine molluscBuccinulum corneum are inhibitors of eukaryotic DNA polymeraseα

Summary The inhibitory effect of esters of p-hydroxybenzoic acid (kelletinins I and A), extracted from the marine gastropodBuccinulum corneum, have been tested on eukaryotic and prokaryotic enzymes of DNA metabolism such as DNA polymerases and , DNA polymerase I, Exo III, pancreatic DNAse I, micrococcal DNAse andE. coli RNA polymerase. Kelletinin I and kelletinin A inhibit preferentially DNA polymerase. The inhibitory effect of kelletinin I involves the hydroxyl group of p-hydroxybenzoic acid.     

Über die Ausscheidung von 3β-Hydroxy-17-Ketosteroiden im Harn von Meerschweinchen

Summary 11-hydroxy-epiandrosterone was isolated and identified from urine of normal untreated female guinea pigs. After cold and hot acid hydrolysis of the urine, we found another 3-hydroxy-17-oxosteroid. Its character was investigated by several methods and we suppose this steroid is9(11)-epiandrosterone, an artificial product of 11-hydroxy-epiandrosterone.     

Hormonal rupture of larval diapause in the tickRhipicephalus sanguineus (Lat.)

Zusammenfassung Die Diapause von Larven der ZeckeRhipicephalus sanguineus (Lat.) wird durch- and-Ecdyson beendet.

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We would like to thank Dr.J. B. Siddal for generously providing-ecdysone, Dr.T. Takemoto for-ecdysone and Dr.N. Krishnan for the juvenile hormone analogue,trans, trans-10, 11-epoxy faresenic acid methyl ester.     

A new indolic antiauxin, α-(5,7-dichloroindole-3-)isobutyric acid: its chemical synthesis and biological activity

Summary A new potent antiauxin, -(5,7-dichloroindole-3-)isobutyric acid has been synthesized and shown to inhibit auxin-mediated elongation ofAvena coleoptiles and to stimulate root growth of rice seedlings. Its activity is stronger than -(p-chlorophenoxy)isobutyric acid and is comparable to that of 2,3,5-triiodobenzoic acid, which are typical antiauxins.     

Zum Mechanismus derβ-Lysin-Mutase-Reaktion

Summary Using tritium labelled substrates it is shown that in the rearrangement of (S) --lysine to 3,5-diaminohexanoic acid catalysed by-lysine mutase a stereospecific hydrogen migration from C-5 to C-6 of the substrate occurs. When the reaction is carried out in the presence of [5-³H]-coenzyme B₁₂, the heavy isotope is transferred both to C-6 of 3, 5-diaminohexanoate and to C-5 of-lysine. In the latter the labelled atom occupies the same diastereotopic position as the H atom that is transferred to C-6 of the product.     

Zur Umwandlung von β-Pyridylcarbinol in Nicotinsäure im tierischen Organismus

Summary By way of the perfusion technique, it is shown that the liver of the rat readily converts-pyridyl-carbinol to nicotinic acid. The turnover attains a rate of 0.5M/g/min.     

Effect of aloe lectin on deoxyribonucleic acid synthesis in baby hamster kidney cells

Summary A homogeneous glycoprotein (mol.wt 40,000) containing 34% carbohydrate was isolated fromAloe arborescens var.natalensis. At a concentration of 5 g/ml, this glycoprotein was shown to stimulate deoxyribonucleic acid (DNA) synthesis in baby hamster kidney (BHK) cells and to have the properties of a lectin which reacts with sheep blood cells. The chemical and physical properties of the glycoprotein (aloe lectin) are also discussed.     

Unterschiedliche Empfindlichkeit verschiedener Angiotensinderivate gegen Abbau durch Plasma oder Nierenhomogenat

Summary -Asp¹-Angiotensin II had a more pronounced action on the blood pressure of nephrectomized rats than the corresponding-compound.-Asp¹-Angiotensins were more slowly destroyed by rat serum, rat kidney homogenate, and human plasma than-compounds, especially-Asp¹-Angiotensin II amide.     

Studio farmacologico di un nuovo coleretico derivato dall'acidoα-cicloesil butirrico

Summary -(1-Hydroxy-4-phenyl-cyclohexyl)butyric acid (M. G. 4833) and-(1-hydroxy-3-phenyl-cyclohexyl) butyric acid (M. G. 4834) have been synthesized; both substances were endowed with choleretic activity.M. G. 4833 is the more active; it acts at lower doses and for a longer time than sodium dehydrocholate on rats, rabbits and dogs submitted to temporary fistulization of the bile-duct.     

Tetrapyrrole biosynthesis from 4,5-dioxovaleric acid inRhodopseudomonas spheroides

Summary Porphyrin biosynthesis from 4,5-dioxovaleric acid was studied in cell suspensions ofR. spheroides. The experiments show that 4,5-dioxovaleric acid is a far precursor of porphyrins through amino laevulinic acid formation in a transamination reaction involving also 1-alanine. It differs radically from the classical aminolaevulinic acid synthesis using glycine and succinyl CoA as substrates.Acknowledgments: The authors are indebted to Dr Rodolfo García for helpful discussions and criticisms. Special thanks are given to Dr Aldo Mitta and other members of the Comisión Nacional de la Energía Atómica for their continuous help and support and for using their facilities in order to synthetise DVA.     

The presence of β-phenylethylamine,p-tyramine,m-tyramine and tryptamine in ganglia and foot muscle of the garden snail (Helix aspersa)

Summary The concentrations of -phenylethylamine,p-tyramine,m-tyramine,m-octopamine and tryptamine in the ganglia or foot muscle ofHelix aspersa range from <0.6 to 11 ng/g.p-Octopamine levels are higher in ganglia (327 ng/g) than in foot muscle (4.1 ng/g). Dopamine and 5-hydroxytryptamine range from 840 to 2710 ng/g while their acid metabolites, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 5-hydroxyindoleacetic acid range from <20 to 130 ng/g.Acknowledgments. We thank Dr A.A. Boulton for helpful discus sion, Dr D.A. Durden for supervising the mass spectrometric analyses, Dr B.A. Davis for the synthesis of the deuterated standards, G.H. Wheatley, E.P. Zarycki and M. Mizuno for expert technical assistance, and Saskatchewan Health and the MRC of Canada for providing financial support.     

Molecular basis of homocysteine toxicity in humans

Because of its similarity to the protein amino acid methionine, homocysteine (Hcy) can enter the protein biosynthetic apparatus. However, Hcy cannot complete the protein biosynthetic pathway and is edited by the conversion to Hcy-thiolactone, a reaction catalyzed by methionyl-transfer RNA synthetase in all organisms investigated, including human. Nitrosylation converts Hcy into a methionine analogue, S-nitroso-Hcy, which can substitute for methionine in protein synthesis in biological systems, including cultured human endothelial cells. In humans, Hcy-thiolactone modifies proteins posttranslationally by forming adducts in which Hcy is linked by amide bonds to -amino group of protein lysine residues (Hcy-N-Lys-protein). Levels of Hcy bound by amide or peptide linkages (Hcy-N-protein) in human plasma proteins are directly related to plasma total Hcy levels. Hcy-N-hemoglobin and Hcy-N-albumin constitute a major pool of Hcy in human blood, larger than total Hcy pool. Hcy-thiolactone and Hcy-thiolactone-hydrolyzing enzyme, a product of the PON1 gene, are present in human plasma. Modification with Hcy-thiolactone leads to protein damage and induces immune response. Autoantibodies that specifically recognize the Hcy-N-Lys-epitope on Hcy-thiolactone-modified proteins occur in humans. The ability of Hcy to interfere with protein biosynthesis, which causes protein damage, induces cell death and elicits immune response, is likely to contribute to the pathology of human disease.Received 30 May 2003; received after revision 21 July 2003; accepted 15 August 2003     

The animal musks and a comment of their biogenesis

Summary The macrocyclic compounds occurring in animal glandular secretions are reviewed. Early hypotheses for their biogenesis from fatty acids via and -oxidations are found to be inadequate. Radio-active acetate was incorporated into macrocyclic ketones of muskrat (Ondatra sp.) preputial glandular secretion, but radiolabelled stearate, oleate, anda, -octadecandioic acid were not incorporated.Acknowledgment. We wish to thank Dr.W.J. Doude van Troostwijk, Research Institute for Nature Management, Arnhem, for his assistance in obtaining muskrats, and Mr J. Vellekoop, Leiden, for the Shakespeare quotations.