Pharmakologische Untersuchungen bei Thiaminmangel I. Änderungen des Katecholamingehalts im Gewebe

Summary (1) The increased tissue catecholamine level of the thiamine deficient rat was shown in the atrium, the ventricle, the brain cortex and in the spleen but not in the brain stem and the adrenal gland. (2) The increased response to tyramine of the thiamine deficient heart is most probably due to the high catecholamine level caused by thiamine deficiency. (3) The increased catecholamine content in the thiamine deficient rat does not result from the increased pyruvic acid.

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Herrn Professor Dr.F. Th. von Brücke zum 60. Geburtstag im Januar 1968 gewidmet.     

Leonurine, an improved synthesis.

Leonurine (1) is the uterotonic principle of Leonurus artemisia. We have developed a simple, high-yield synthetic procedure of 1 that is adaptable to large scale preparation. The synthesis involves the condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of DDC using 1:1 HMPT-ether as solvent. The synthetic leonurine showed uterotonic activity in vivo and in vitro.     

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the α-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes. Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and α-oxidation has not been studied, nor have possible adverse effects of deficient α-oxidation been considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured cells and animal models showed that α-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested that some pathological consequences of thiamine starvation could be related to impaired α-oxidation. Whereas accumulation of phytanic acid and/or 2-hydroxyfatty acids or their α-oxidation intermediates in TRMA patients given a normal supply of thiamine is unlikely, this may not be true when malnourished. Received 23 December 2005; received after revision 10 April 2006; accepted 28 April 2006     

Thiamine-quinone adducts. Colorimetric determination of thiamine

Summary 2, 3-dichloro-1,4-naphtoquinone reacts with thiamine in the presence of NH₃ to give a 12 adduct, for which structureII is proposed on the basis of analytical and spectroscopic (IR) data. Such a reaction is very useful for thiamine quantitative determination.     

The metabolism of dibenz[b,f]-1,4-oxazepine (CR): in vivo hydroxylation of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one and the NIH shift

Studies of the in vivo metabolism of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one (2) specifically deuteriated at C7 implicate an arene oxide intermediate during the conversion to 7-hydroxy-2 (4) as evidenced by the observation of the NIH shift.     

Naphthoquinone derivatives from the fungusHendersonula toruloidea

Summary 2 yellow naphthoquinone derivatives were isolated from several pathogenic strains ofHendersonula toruloidea Nattrass. They were identified as 2,7-dimethoxy-6-ethyl-5-hydroxy-1,4-naphthoquinone and 2,7-dimethoxy-5-hydroxy-6-(1-acetoxyethyl)-1,4-naphthoquinone by means of physico-chemical methods.Thanks are due to Mr A.J.M. van Beijnen, Laboratory for Organic Chemistry, State University of Utrecht, for optical rotation measurements.The authors are indebted to Mr C. Versluys, Analytical Laboratory, State University of Utrecht, for measuring the mass spectra.We thank Mr J. W. Marsman, Institute for Organic Chemistry TNO, Utrecht, for the PMR-spectra.     

The adequacy of thiamine in liquid diets used in animal models of alcoholism

Summary The effects of chronic administration of 2 types of liquid diets on brain thiamine pyrophosphate (TPP) levels have been investigated. With the Lieber-DeCarli diet, rats in the control group had significantly lower TPP levels compared with those of the ethanol group. The Nutrament diet used in mice was apparently adequate in the thiamine supply.Acknowledgment. The authors are thankful to Dr Hebe Greizerstein for her review and comments on this mansucript.     

Inhibition of thiamine transport in baker's yeast by methylene blue

Summary Methylene blue was found to inhibit thiamine transport competitively (K_i=0.63 M) in baker's yeast. The dye was also effective in abolishing the growth inhibition ofSaccharomyces cerevisiae by pyrithiamine which is known to be taken up by a common transport system for thiamine in yeast cells. A possible mechanism for the inhibition by methylene blue of the thiamine transport system in baker's yeast is discussed.     

The male pheromone of the old house borerHylotrupes bajulus (L.) (Coleoptera: Cerambycidae): Identification and female response

We report here the identification of the long-range, male-produced sex pheromone of the Old house borerHylotrupes bajulus. Chemical analysis of hexane extracts obtained by surface extraction from dissected prothoracic glands and from headspace samples of the two sexes, revealed male-specific compounds: (3R)-3-hydroxy-2-hexanone, 2-hydroxy-3-hexanone, the diastereomeric diols (2R, 3R)-2,3-hexanediol and (2S, 3R)-2,3-hexanediol, 2,3-hexanedione, as well as 1-butanol.In wind tunnel bioassays we tested the influence of these male-specific compounds from the prothoracal glands on the behaviour of unmated and mated females. Specific behavioural sequences of the tested females (activity, running behaviour, searching, cleaning, flying, extension of ovipositor) were recorded. Unmated females were attracted by male beetles, headspace extracts of males, synthetic blends of the major pheromone compounds as well as by the components (3R)-3-hydroxy-2-hexanone, and the diastereomeric diols. Hexane, female beetles and 2,3-hexanedione did not attract unmated females. The reactions of mated females to male beetles and headspace samples did not differ significantly from those of the controls.The results of the bioassays show that the two-stage premating behaviour is initiated by emission of a long-range sex pheromone from the male prothoracal glands, which functions as an activator, attractant, and possibly aphrodisiac for unmated females.     

Thiamine triphosphate metabolism and its turnover in the rat liver

Summary When rats were injected with a thiamine disulfide derivative, the content of thiamine triphosphate (TTP) in the liver doubled within 3 h after a preceeding rise in thiamine pyrophosphate; it then returned to the basal level within the next 3h, indicating a net increase of TTP in vivo and its rapid turnover.     

Effect of thiamine hydrochloride on the blood level of 2-formyl 1-methyl pyridinium oxime chloride (2-PAM.C1) in rats.

The biological half-life of 2-PAM.C1 was found to increase in female rats pretreated with thiamine hydrochloride (10 mg/kg i.m.). No such effect was observed in the male rats.     

Thiamine-binding activity of Saccharomyces cerevisiae plasma membrane

The specific binding activity to [14C]thiamine was found to be located in hte plasma membrane of Saccharomyces cerevisiae. The activity was inhibited by several thiamine analogs and it was hardly detectable in the plasma membrane from a thiamine transport mutant of Saccharomyces cerevisiae. Some properties of the thiamine-binding activity of yeast plasma membrane are discussed in connection with those of the thiamine transport system.     

Creatol (5-hydroxycreatinine), a new toxin candidate in uremic patients

Both 5-hydroxy-1-methylhydantoin (3) and the hitherto unrecognized 5-hydroxycreatinine (2-amino-5-hydroxy-1-methyl-imidazol-4(5H)-one or creatol) (6) can be isolated from the urine of uremic patients, in whom these compounds probably arise as oxidative metabolites of creatinine (1). The enhanced production of the well-known uremic toxin, methylguanidine (8), from creatinine (1) in such patients, almost certainly occurs via the newly recognized metabolite.     

Antiarrhythmic properties of 3-(2-hydroxy-3 isopropylamino-propoxy)-3 phenyl-2 isoindolinone-1, (RS, SR) in the dog]

In the Dog, 3-(2-hydroxy-3 isopropylamino-proxy)-2-phenyl-1-isoindolinone (RS, SR) possesses an anti-arrhythmic activity similar to that of quinidine but at dose levels 2 to 6 times lower than in the case of the latter compound. Furthermore, in contrast to quinidine, at the dose levels where the antiarrhythmic activity is well observed, the compound is devoid of hypotensive activity and of depressive action on cardiac contractility. The first clinical studies of this compound have shown its usefulness in the treatment of ventricular and supraventricular arrhythmias.     

Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

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 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 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 less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-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.     

Occurrence of thiaminase II inSaccharomyces cerevisiae

Summary It was found that cell-free extracts ofSaccharomyces cerevisiae contain thiaminase II which hydrolyzes thiamine and thiamine analogs. The possible involvement of this enzyme and thiamine-synthesizing enzymes in thiamine production from thiamine antagonists is discussed.30 September 1986Acknowledgments. We thank the late Dr S. Yurugi, Takeda Pharmaceutical Industries, Osaka, for his generous gifts of dimethialium, 2-northiamine, -hydroxyethylthiamine, hydroxymethylpyrimidine, 2-norhydroxymethylpyrimidine and hydroxyethylthiazole. We also thank Prof. H. Nakayama, Yamaguchi Women's College, for his kind supply ofEscherichia coli 70–17 and 26–43.     

Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals

In most organisms, the main form of thiamine is the coenzyme thiamine diphosphate. Thiamine triphosphate (ThTP) is also found in low amounts in most vertebrate tissues and can phosphorylate certain proteins. Here we show that ThTP exists not only in vertebrates but is present in bacteria, fungi, plants and invertebrates. Unexpectedly, we found that in Escherichia coli as well as in Arabidopsis thaliana, ThTP was synthesized only under particular circumstances such as hypoxia (E. coli) or withering (A. thaliana). In mammalian tissues, ThTP concentrations are regulated by a specific thiamine triphosphatase that we have recently characterized. This enzyme was found only in mammals. In other organisms, ThTP can be hydrolyzed by unspecific phosphohydrolases. The occurrence of ThTP from prokaryotes to mammals suggests that it may have a basic role in cell metabolism or cell signaling. A decreased content may contribute to the symptoms observed during thiamine deficiency.Received 7 March 2003; received after revision 11 April 2003; accepted 14 April 2003     

Thiamine-binding activity ofSaccharomyces cerevisiae plasma membrane

Summary The specific binding activity to [¹⁴C]thiamine was found to be located in the plasma membrane ofSaccharomyces cerevisiae. The activity was inhibited by several thiamine analogs and it was hardly detectable in the plasma membrane from a thiamine transport mutant ofSaccharomyces cerevisiae. Some properties of the thiamine-binding activity of yeast plasma membrane are discussed in connection with those of the thiamine transport system.     

Reversal of pyrithiamine-induced growth inhibition of Saccharomyces cerevisiae by oxythiamine

Oxythiamine reversed the growth inhibition of Saccharomyces cerevisiae caused by pyrithiamine, although oxythiamine alone inhibited yeast cell growth. This phenomenon was explained by thiamine production from these 2 thiamine antagonists which was demonstrated using cell suspensions and the crude extract of S. cerevisiae.     

Marine eicosanoids: Occurrence of 8-(R)-HETE in the starfishPatiria miniata

Summary The first isolation of 8-(R)-hydroxy-5Z, 9E, 11Z, 14Z-eicosatetraenoic acid [8-(R)-HETE] from a marine source, the pacific starfishPatiria miniata, is reported. 8-(R)-HETE occurs together with 8-(R)-hydroxy-5Z, 9E, 11Z, 14Z, 17Z-eicosapentaenoic acid.