Mechanism of aluminium-induced porphyrin synthesis in bacteria

In previous studies, aluminium was found to retard bacterial growth and enhance porphyrin formation in Arthrobacter aurescens RS-2. The aim of this study was to establish the mechanism of action of aluminium which leads to increased porphyrin production. Cultures of Arthrobacter aurescens RS-2 were incubated in the absence and presence of 0.74 mm aluminium. After 6 and 24 h of incubation, various parameters of the haem biosynthetic pathway were determined. After 6 h of incubation with aluminium, the activities of the enzymes aminolevulinate synthase (ALAS), aminolevulinate dehydratase (ALAD), porphobilinogen deaminase (PBGD) and uroporphyrinogen decarboxylase (UROD) were increased by 120, 170, 190 and 203%, respectively, while that of ferrochelatase (FC) was found to be unchanged. However, after 24 h of incubation, no change in the activities of ALAS and ALAD was noted, while an about 2-fold increase in PBGD and UROD activities were observed. FC activity was decreased by 63%. It was concluded that aluminium exerts its effect by inducing the enzymes PBGD and UROD rather than by a direct or indirect effect on ALAS. Its effect on the final step in the haem biosynthetic pathway is discussed.     

Cleavage of double-stranded DNA by manganese tris(methylpyridiniumyl)porphyrin linked to 3′-spermine oligonucleotides

 Cleavage of double-stranded DNA was performed with cationic manganese porphyrin complexes linked via a spermine tether to the 3′- or 5′-side of triple-helix-forming oligonucleotides (cleaver-TFO conjugates). The targeted sequence was a 15-polypurine sequence present in the env gene of HIV-1 (positions 7301–7315). The presently used TFOs contain only thymine and 5-methylcytosine residues and one adenine at the 3′-end in order to be able to easily introduce a 3′-polyamine linker by reductive amination of the corresponding 3′-apurinic polypyrimidine oligonucleotides. With this method we prepared these TFO-cleaver conjugates in 45% yield with only two equivalents of the Mn-TrisMPyP-COOH precursor. These new metalloporphyrin-TFO conjugates were able to cleave a complementary 45-mer duplex at 10 nM concentration with only ten equivalents of TFO-cleaver. Conjugates without spermine, without 5-methylcytosine, with a random sequence or with the managanese porphyrin-spermine entity on the 5′-end of TFOs were synthesized for comparative studies. Received: 6 December 1995 / Accepted: 5 February 1996     

Nω-Hydroxyamino-α-amino acids as a new class of very strong inhibitors of arginases

 The effects of various compounds bearing an N-OH group such as N-hydroxy-guanidines, amidoximes, and hydroxylamines, on bovine and rat liver arginases was studied. Some of these compounds with an l-α-amino acid function at an appropriate distance from the N-OH group acted as strong competitive liver arginase inhibitors, displaying Ki values between 4 and 150 μM. Two compounds, N ^ε-hydroxy-l-lysine and N ^ω-hydroxy-d,l-indospicine, which exhibited Ki values of 4 and 20 μM (at pH 7.4), were the most potent inhibitors of arginase described to date. The distance between the α-amino acid and N-OH functions appeared to be crucial for potent inhibition of arginase, as N ^δ-hydroxy-l-ornithine, which has one -CH₂ group less than N ^ε-hydroxy-l-lysine, exhibited a 37-fold higher Ki value than N ^ε-hydroxy-l-lysine. Based on these results, a model for the interaction of N ^ω-hydroxyamino-l-α-amino acids with the arginase active site is proposed. This model involves the binding of the N-OH group of the inhibitors to the arginase Mn(II) center and suggests that N ^ε-hydroxy-l-lysine is a good transition state analog of arginase.     

Light,iron, Sam Granick and the origin of life

Living matter is an organized system which requires a continual flux of energy for its survival. As a working assumption, the flux of energy required for the origin of a self-duplicating cell is taken as the power required for the maintenance of a modern cell: 10 mW per g of carbon or some 10⁵ times the output per gram of the sun. Solar photochemistry supplies the energy for the continuing evolution of life and, by continuity, for its origin. The iron oxide-sulfide photosynthetic unit proposed by S. Granick 35 years ago was meant to supply this energy. The evolution of complex organic photosensitizers is rationalized by the Granick hypothesis that biosynthetic pathways recapitulate their evolution. These concepts are discussed in the context of the evolution of photosynthetic systems and the known properties of these pigments.     

The effect of silicon on the manganese nutrition of soybeans (Glycine max (L.) Merrill)

Summary Silicon during the early vegetative stage did not affect the oven dry weight of any of the various tissues of the soybean plant. Silicon did, however, decrease the Mn concentration in the youngest fully mature leaf at intermediate levels of Mn. This effect did not occur at the lowest or highest Mn levels. Deficiency and toxicity symptoms were moderated to a slight degree by Si except at the highest level of Mn.     

Porphyrins in the perienteric fluid of Ascaris lumbricoides.

Cain G. D. and Bassow F. 1976. Porphyrins in the perienteric fluid of Ascaris lumbricoides. International Journal for Parasitology6: 79–82. Porphyrins in the perienteric fluid of adult female A. lumbricoides were esterified in methanolic H₂SO₄, extracted in chloroform, separated by thin-layer chromatography, and identified spectrophotometrically before and after conversion to their zinc and copper chelates. Protoporphyrin IX was the major component, comprising 95·4% of the total; the remaining 4·6 % was coproporphyrin III. Uroporphyrin was not detected; no porphyrins were recovered from other worm tissues. Fluid from worms with light and dark colored guts varied in protoporphyrin content from 0·58 to 4·08 nmoles/ml, respectively, but fluid from both groups contained similar molar ratios of protoporphyrin, coproporphyrin and heme.     

Membrane‐Free Zn/MnO2 Flow Battery for Large‐Scale Energy Storage

The traditional Zn/MnO₂ battery has attracted great interest due to its low cost, high safety, high output voltage, and environmental friendliness. However, it remains a big challenge to achieve long‐term stability, mainly owing to the poor reversibility of the cathode reaction. Different from previous studies where the cathode redox reaction of MnO₂/MnOOH is in solid state with limited reversibility, here a new aqueous rechargeable Zn/MnO₂ flow battery is constructed with dissolution–precipitation reactions in both cathodes (Mn²⁺/MnO₂) and anodes (Zn²⁺/Zn), which allow mixing of anolyte and catholyte into only one electrolyte and remove the requirement for an ion selective membrane for cost reduction. Impressively, this new battery exhibits a high discharge voltage of ≈1.78 V, good rate capability (10C discharge), and excellent cycling stability (1000 cycles without decay) at the areal capacity ranging from 0.5 to 2 mAh cm^‐2. More importantly, this battery can be readily enlarged to a bench scale flow cell of 1.2 Ah with good capacity retention of 89.7% at the 500th cycle, displaying great potential for large‐scale energy storage.     

Influence of manganese exposure on cognitive function,plasma APP and Aβ levels in older men

BackgroundElevated manganese (Mn) exposure impairs cognition in adults and children, but the association between Mn and cognitive function in elderly people is unclear. Previous studies have linked Mn neurotoxicity in AD to Aβ-dependent mechanisms. However, the association between Mn and plasma APP and Aβ in the general elderly population remains unknown. This study aimed to investigate the association between Mn exposure and cognitive function, plasma APP and plasma Aβ in older adults.MethodsCognitive abilities in 375 men aged 60 and older in Guangxi, China were assessed using the Mini-Mental State Examination (MMSE) and cognitive impairment were identified using education-stratified cut-off points of MMSE scores. Urinary Mn levels and plasma APP, and Aβ levels were measured using ICP-MS and ELISA, respectively.ResultsA total of 109 (29.07 %) older men were identified as having cognitive impairment. The median urinary Mn level was 0.22 μg/g creatinine. Urinary Mn levels were negatively correlated with MMSE scores (β = −1.35, 95 % CI: −2.65 to −0.06; p = 0.041). In addition, higher concentrations of urinary manganese were associated with a greater risk of cognitive impairment (OR = 2.03, 95 % CI: 1.14–3.59; comparing the highest and lowest manganese; p = 0.025). Moreover, plasma APP levels were inversely associated with urinary Mn levels (r = −0.123, p = 0.020), and positively associated with MMSE scores (r = 0.158, p = 0.002). Surprisingly, no correlations were observed between plasma Aβ42, Aβ40, Aβ40/Aβ42, or Aβ42/Aβ40 and urinary Mn levels and MMSE scores.ConclusionThese results suggested that Mn exposure is negatively associated with older men’s cognition and plasma APP levels, but not plasma Aβ levels.     

Canopy throughfall links canopy epiphytes to terrestrial vegetation in pristine conifer forests

To what extent does epiphytic community composition in boreal forests reflect soil nutrient status? To answer this question, we investigated potential links between terrestrial plants and lichen-dominated communities in Picea glauca x engelmannii canopies in south-central British Columbia. We combined original data on vegetational composition in the ground and tree layers with published data on elemental uptake in standardized transplants of the lichen Lobaria pumonaria affixed to the lower branches of studied trees. Procrustean association metrics revealed a significant concordance between community composition among the epiphytic and terrestrial vegetation, which was stronger in Mn-enriched conifer canopy settings, and weaker within the cation-enriched dripzones of adjacent Populus trees. We also found that the NMDS1-gradient for each vegetation layer was strongly correlated with base cations (and inversely with Mn) in canopy throughfall, as well as with soil and bark pH. We conclude that elemental composition in canopy throughfall forms a functional link between terrestrial and epiphytic vegetation.     

Bioavailability of metalloporphyrin-based SOD mimics is greatly influenced by a single charge residing on a Mn site

Abstract

In the cell Mn porphyrins (MnPs) likely couple with cellular reductants which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to three orders of magnitude depending upon the length of alkylpyridyl chains and type of isomer. The effects result from the interplay of solvation, lipophilicit and stericity. Impact of ascorbate on accumulation of MnPs was measured in E. coli and in Balb/C mouse tumours and muscle; for the latter measurements, the LC/ESI-MS/MS method was developed. Accumulation was significantly enhanced when MnPs were co-administered with ascorbate in both prokaryotic and eukaryotic systems. Further, MnTnHex-2-PyP⁵⁺ accumulates 5-fold more in the tumour than in a muscle. Such data increase our understanding of MnPs cellular and sub-cellular accumulation and remarkable in vivo effects. The work is in progress to understand how coupling of MnPs with ascorbate affects their mechanism of action, in particular with respect to cancer therapy.