Caffeine derivatives of haematin compounds

1. Caffeine reacts with haematin to form a caffeine-haematin compound that has a characteristic absorption spectrum. 2. Graphical analysis of the titration of haematin with caffeine shows that 2mol.prop. of caffeine split the dimeric haematin. 3. Thermodynamic parameters suggest that the reaction involves the making and breaking of hydrophobic bonds. 4. Graphical analysis shows dimeric haem to be split by 2mol.prop. of caffeine to yield a compound with an unusual multibanded absorption in the Soret region. 5. It is postulated that the linkage between the haem groups of dimeric haem and the haematin groups of dimeric haematin is essentially hydrophobic in nature.     

Microbial oxidation of dehydroepiandrosterone and related compounds.

The oxidation of dehydroepiandrosterone (DHEA), 4-androstene-3, 17-dione, and estrone with Streptomyces roseochromogenes NRRL B-1233 was studied. The oxidation products were isolated and identified as as 16alpha-hydroxy-DHEA, 16alpha-hydroxy-4-androstene-3,17-dione and 16alpha-hydroxyestrone. The yields of these three products were 85%, 41% and 18%, respectively. This indicates the substrate stereospecificity of 16alpha-hydroxylase of the organism. An interrelationship between cell growth and the formation of 16alpha-hydroxylated steroid was observed in any case. For formation of 16alpha-hydroxy-DHEA, 16alpha-hydroxylase showed good activity at DHEA concentration of 3.47 x 10(-4)M. In the case of DHEA, 16alpha-hydroxy-4-androstene-3,17-dione and 5-androstene-3beta, 16alpha, 17beta-triol were obtained after the yield of 16alpha-hydroxy-DHEA reached the maximum yield for about 30 hr. The oxidation pathway of DHEA is discussed.     

Effects of arginine homologous and other guanidino compounds on the ATP level and glucose oxidation in isolated fat cells.

The arginine homologues 2-amino-3-guanidinopropionic acid, 2-amino-4-guanidino-butyric acid and 2-amino-6-guanidinocaproic acid (= homoarginine) were synthesized and transformed into their methyl esters. The latter, together with arginine methyl esters. The latter, together with arginine methyl ester, arginine diethylamide and some guanidino compounds without the arginyl structure (agmatine, isopentyl-guanidine and n-butylbiguanide) were examined with regard to their behaviour on isolated fat cells, concerning the adrenalin-induced depression of the ATP level and the stimulation of glucose oxidation. The homoarginyl and arginyl derivatives counteracted the effect of adrenalin by re-elevating the ATP level, and thus they exerted an insulin-like activity. The esters were slightly active, whereas the arginine diethylamide and agmatine had a marked effect. The shorter homologues of arginine were totally inactive. However isopentyl-guanidine and butylbiguanide followed the effect of adrenalin: they additionally lowered the ATP level and therefore they acted in opposition to insulin. For comparative reasons the same compounds were tested with regard to their effects on glucose oxidation. The results were consistent with those quoted above: the homoarginyl and arginyl derivatives (agmatine included) forced the glucose oxidation similarly to insulin, the shorter homologues were inactive, isopentylguanidine and butylbiguanide decreased it.     

Enzyme-catalysed conjugations of glutathione with unsaturated compounds

1. Rat-liver supernatant catalyses the reaction of diethyl maleate with glutathione. 2. Evidence is presented that the enzyme involved is different from the known glutathione-conjugating enzymes, glutathione S-alkyltransferase, S-aryltransferase and S-epoxidetransferase. 3. Rat-liver supernatant catalyses the reaction of a number of other αβ-unsaturated compounds, including aldehydes, ketones, lactones, nitriles and nitro compounds, with glutathione: separate enzymes may be responsible for these reactions.     

Differentiation between C- and O-glycosyl compounds

A method for distinguishing between C-glycosyl compounds and O-glycosides depending on the acid stability of the borohydride reduction products of periodate-oxidized compounds has been examined and found to give equivocal results. The method can, however, be of value in determining the structure of the glycosyl residue. Examination of NMR spectra and the products of methylation have established the C-glycosyl nature of orientin and iso-orientin.     

The kinetics of the recombination reaction between apomyoglobin and alkaline haematin.

Apomyoglobin was prepared by an extremely mild modification of the acid/butanone technique, and the kinetics of the recombination reaction between this preparation and alkaline haematin were studied. The recombination has been shown to be precisely second-order and mono-phasic. Rate constants obtained from the study are in good agreement with values obtained previously by an indirect technique not involving separation of haem and apoprotein.     

Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides

Dithiocarbamate (DTC)-based pesticides have been implicated in Parkinson’s disease (PD) through epidemiological links to increased risk of PD, clinical reports of parkinsonism following occupational exposure to the DTC-based pesticide maneb, and experimental studies showing dopaminergic neurodegeneration with combined exposure of rats to maneb and paraquat. We hypothesize that the manganese-ethylene-bis-dithiocarbamate (MnEBDC) complex in maneb may produce oxidative stress by catalyzing catechol oxidation. We tested this hypothesis by performing a structure-function analysis of metal-EBDC and metal-diethyldithiocarbamate (DEDC) complexes of Mn²⁺, Zn²⁺, and Cu²⁺ to catalyze oxidation of N-acetyldopamine (NA-DA) and 3,4-dihydroxyphenylacetic acid (DP) in the presence and absence of N-acetylcysteine (NAC), a model of glutathione. Both Mn-DTCs retained the capacity of the parent ion to catalyze one-electron oxidation of NA-DA, but lost the ability to catalyze DP oxidation. Strikingly, while Zn²⁺ did not catalyze catechol oxidation, both Zn-DTCs catalyzed one-electron oxidation of NA-DA but not DP. While Cu²⁺ catalyzed oxidation of both catechols, Cu-DTCs were inert. Similar results were obtained with MnEBDC and dopamine or norepinephrine; however, zinc-ethylene-bis-dithiocarbamate was less efficient at catalyzing oxidation of these catechols. Our results point to the potential for manganese- and zinc-containing EBDC pesticides to promote oxidative stress in catecholaminergic regions of the brain.     

Catalysis of aerobic olefin oxidation by a ruthenium perhaloporphyrin complex

The perhalogenated porphyrin ruthenium complex (TFPPCl₈)Ru(CO) (TFPPCl₈ = octachlorotetrakis(pentafluorophenyl)porphyrin) catalyzes aerobic oxidation of olefins at room temperature. Cyclohexene is oxidized primarily at the allylic position, and styrene primarily to benzaldehyde, indicating a radical autoxidation mechanism. Reactions are enhanced by visible light. Reaction with _m-chloroperbenzoic acid converts the ruthenium complex to (TFPPCl₈)Ru(O)₂, but such oxo complexes do not appear to participate in catalytic aerobic oxidation.     

Evidence of the oxidation of unsaturated fatty acids in cataracts

Gas chromatography analysis with the use of an electron captured detector including preparation of the halogen-substituted derivatives of fatty acids is a useful tool for the detection of lipid peroxidation products both in vitro and in vivo. This technique was applied to determine the content of fatty acid oxy-derivatives in lipid samples of transparent and completely opaque human lenses. At the stage of mature cataract a significantly increased level of oxyproducts was observed in the lens lipid fraction. It was concluded that accumulation of polar oxygroups in the lipid bilayer of plasma membranes of lens fibres is a plausible cause of their damage in cataracts.