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Associations between multiple essential trace metal concentrations and risk of hyperuricemia: insights from a central Chinese population.

Previous studies have indicated that levels of individual essential trace metals are related to hyperuricemia (HUA), but evidence on their combined effects is limited. To address this gap, the associations of individual and joint levels of 12 essential trace metals (manganese, selenium, nickel, chromium, cobalt, tin, iron, molybdenum, zinc, strontium, vanadium, and copper) with the risk of HUA were investigated in 2,021 adults recruited from Hunan Province, China. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine urinary metal concentrations. Logistic regression, Bayesian kernel machine regression (BKMR), and quantile g calculation (Qgcomp) were applied to evaluate the associations of single and mixture metal concentrations with HUA. Of the participants, 516 (25.53%) were diagnosed with HUA. Inverse associations were found between vanadium, chromium, manganese, iron, cobalt, selenium, strontium, and molybdenum levels and HUA, with ORs ranging from 0.63 to 0.91. Conversely, a positive association was observed between zinc concentration and HUA [OR (95% CI): 1.17 (1.01, 1.37)]. Both BKMR and Qgcomp models showed a negative overall effect of essential trace metals on HUA risk, with strontium (- 43.6%) and vanadium (- 27.8%) being the main contributors. In addition, formal interaction tests revealed significant effect modification by age for tin and by BMI for zinc. In conclusion, the levels of essential trace metals were linked to a decreased risk of HUA, and these associations were modified by age and BMI only for specific metals.

Humans

Trace metal and essential fatty acid deficiency during total parenteral nutrition.

While deficiences of trace metals and essential fatty acids are rare in humans fed orally, the widespread use of total parenteral nutrition (TPN) has increased the likelihood of encountering these deficiences. A 14-year-old boy, with total villous atrophy of the small intestine, suffered from severe malnutrition and was placed on a conventional TPN regimen. Although not immediately recognized, he rapidly developed deficiencies of zinc, copper and essential fatty acids. Careful monitoring of the course of the illness and the responses to sequential treatments with zinc, lipid, and copper given intravenously allowed examination of the effects of the deficiencies on skin, intestine, liver, and hemopoietic systems and helped to establish normal requirements for the metals. The progress of the illness suggested that patients with intestinal malabsorption may be especially at risk of developing some of these lesser known complications of TPN.

Adolescent

The Elements of Life, Photosynthesis and Genomics.

I am a Professor of Biochemistry, Biophysics and Structural Biology and Plant and Microbial Biology at the University of California in Berkeley. I was born and raised in India, emigrated to the United States to attend university, earning a B.S. in Molecular Biology and a Ph.D. in Biochemistry at the University of Wisconsin in Madison. Following post-doctoral studies with Lawrence Bogorad at Harvard University where I became interested in genetic control of trace element quotas, I joined the department of Chemistry and Biochemistry at UCLA. One of the first to appreciate essential trace metals as potential regulators of gene expression, I articulated the details of the nutritional Cu regulon in Chlamydomonas. In parallel, I used genetic approaches to discover the genes governing missing steps in tetrapyrrole metabolism, including the attachment of heme to apocytochromes in the thylakoid lumen and the factors catalyzing the formation of ring V in chlorophyll. After biochemistry and classical genetics, I embraced genomics, taking a leadership role on the Joint Genome Institute's efforts on the Chlamydomonas genome and more recently, contributing to high quality assemblies of several genomes in the green algal radiation, and large transcriptomic and proteomic datasets - focusing on the diel metabolic cycle in synchronized cultures and acclimation to key environmental and nutritional stressors - that are well-used and appreciated by the community. A new venture in Berkeley is the promotion of Auxenochlorella protothecoides as the true "green yeast" and as a platform for engineering algae to produce useful bioproducts.

Photosynthesis

The biological relevance of potentially toxic metals in freshwater fish.

Trace elements are essential for a number of physiological functions including oxygen transfer, enzymatic reactions and antioxidant protection of the animal organism. Elevated concentrations outside the physiological optimum, on the other hand, can cause undesirable health complications, disrupt metabolic pathways, reproductive capacity, or oxidative balance. The negative anthropogenic impacts on the environment are alarming and the impacts on the aquatic environment have been increasing disproportionately in recent years. Against this background, all potential threats to biota need to be explained and better understood, the possible risks need to be better informed and understood, and a balance needs to be struck between the fundamental nature and the harmful effects of these metals. This mini-review examines the roles of potentially toxic metals including cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo) and zinc (Zn) in fish physiology. This document also elucidates the mechanisms underlying the assessment of regulatory processes, the potential negative consequences of overexposure, the interactions of these metals on fish health, and in the environmental context.

biomarker

Microbial membrane transporters reveal trace metal niche adaptation in distinct water masses of the Southern Ocean.

BACKGROUND: Trace metals are co-factors for enzymes that are essential for microbial metabolism and the cycling of major elements. Membrane transporters allow microbes to sense and react to trace elements in the environment and to balance their uptake and export for the regulation of intracellular metal homeostasis. The acquisition and efflux of trace metals could lead to reciprocal feedbacks between microbes and the surrounding environment. Whether these processes vary among trace metals and across habitats is presently not known. We used membrane transporters into and out of the cell as indicators for the uptake and efflux of trace metals and provide a detailed picture of the distribution of the respective genes in distinct provinces in surface waters and in subsurface water masses across a transect in the Southern Indian Ocean. RESULTS: We observed marked spatial and vertical patterns in normalized gene abundances of transporters of iron (Fe), manganese (Mn), nickel (Ni) and copper (Cu). Changes in gene abundances were specific to the type of transporter and trace metal, and pronounced differences between surface and specific water masses emerged. We found an enrichment in genes related to efflux and homeostasis of Fe, Ni and Cu in two water masses of the deep ocean that are North Atlantic Deep Water (NADW) and Lower Circumpolar Deep Water (LCDW). This pattern was observed on the community level and for metagenome-assembled genomes (MAGs) affiliated with Alteromonadaceae and Burkholderiaceae that were abundant in these two water masses. CONCLUSIONS: The enrichment in trace metal efflux and resistance genes points to microbially mediated processes, exerted by homeostasis, with potential influence on the trace metal speciation and distribution in specific water masses in the deep ocean. The gene repertoire and distinct distribution pattern of the taxa identified as potential key players could reflect an adaptation to these old water masses with trace metals acting as selective driver. Video Abstract.

Membrane Transport Proteins

Association of urinary levels of trace metals with type 2 diabetes and obesity in postmenopausal women in Korea: A community-based cohort study.

Several toxic metals have been associated with metabolic diseases like obesity and diabetes mellitus (DM) in humans. However, knowledge regarding the influence of many trace elements, especially in combination with essential elements is limited. This study aims to address this research gap by investigating the associations of both non-essential and essential inorganic trace elements in urine with DM and obesity, employing a group of postmenopausal women (n = 851) from the Korean Genome and Epidemiology Study (KoGES) cohort. Urine samples were collected during 2017-2018, and were analyzed for 19 trace elements using inductively coupled plasma-mass spectrometry and an automatic mercury analyzer. Outcomes of interest were metabolic diseases (DM and obesity) and DM-related traits (insulin resistance and β-cell function). After adjustment of covariates, such as age, alcohol consumption, smoking status, educational level, and daily energy intake, urinary Zn, Ni, Tl, and U levels were associated with the prevalence of DM and homeostatic model assessment (HOMA) for insulin resistance (IR) in the postmenopausal women. In the whole mixture model, however, no significant association was observed for the prevalence of DM. Urinary levels of Zn were negatively associated with HOMA of β-cell function (HOMA-β), positively correlated with HbA1c levels, HOMA-IR, and prevalent DM. In addition, urinary Zn, Co, Tl, and Cs were positively associated with obesity (body mass index ≥25 kg/m2). The present observation shows that several individual elements and their mixtures may be associated with the prevalence of DM, IR, or obesity.

Humans

Recognition of metal cations by biological systems.

Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once.

Animals

The role of vanadium in green plants. III. Influence on cell division of Chlorella.

Vanadium, although essential for growth and chlorophyll formation in unicellular green algae, reveals toxic influences on cell division of Chlorella pyrenoidosa, these disturbances arising in the same range of V-concentrations as the known positive effects of the trace metal. In permanent light, as documented by cell volume statistics, vanadium (4-10(-7) g-at/1 as NH4VO3) causes a significant shift of the distribution maxima to higher values of the algal cell volume, the shift having its optimum at 10(-5) g-at V/1. It is documented in pH-constant liquid culture that this effect is not due to a change of pH in the nutrient medium. Under synchronous conditions of algal cultivation (16:8h), vanadium causes a total arrest of cell division after 3 periods; this stop lasts for the next 3 cycles. Afterwards, asynchronous divisions newly occur and lead to generally larger autospores. Staining of algal cell nuclei revealed an inhibitory V-effect on nuclear division, yielding giant nuclei with multiple sets of chromosomes, and thereby limiting cell division. Under these conditions, Chlorella pyrenoidosa is not synchronizable in presence of vanadium.

Cell Division

A novel Alteromonas phage with tail fiber containing six potential iron-binding domains.

Viruses play a vital role in regulating microbial communities, contributing to biogeochemical cycles of carbon, nitrogen, and essential metals. Alteromonas is widespread and plays an essential role in marine microbial ecology. However, there is limited knowledge about the interactions of Alteromonas and its viruses (alterophages). This study isolated a novel podovirus, vB_AmeP-R22Y (R22Y), which infects Alteromonas marina SW-47 (T). Phylogenetic analysis suggested that R22Y represented a novel viral genus within the Schitoviridae family. R22Y exhibited a broad host range and a relatively large burst size, exerting an important impact on the adaptability and dynamics of host populations. Two auxiliary metabolic genes, encoding Acyl carrier protein and AAA domain-containing protein, were predicted in R22Y, which may potentially assist in host fatty acid metabolism and VB12 biosynthesis, respectively. Remarkably, the prediction of the R22Y tail fiber structure revealed six conserved histidine residues (HxH motifs) that could potentially bind iron ions, suggesting that alterophages may function as organic iron-binding ligands in the marine environment. Our isolation and characterization of R22Y complements the Trojan Horse hypothesis, proposes the possible role of alterophages for marine iron biogeochemical cycling, and provides new insights into phage-host interactions in the iron-limited ocean.IMPORTANCEIron (Fe), as an essential micronutrient, is often a limiting factor for microbial growth in marine ecosystems. The Trojan Horse hypothesis suggests that iron in the phage tail fibers is recognized by the host's siderophore-bound iron receptor, enabling the phage to attach and initiate infection. The potential role of phages as iron-binding ligands has significant implications for oceanic trace metal biogeochemistry. In this study, we isolated a new phage R22Y with the potential to bind iron ions, using Alteromonas, a major siderophore producer, as the host. The tail fiber structure of R22Y exhibits six conserved HxH motifs, suggesting that each phage could potentially bind up to 36 iron ions. R22Y may contribute to colloidal organically complexed dissolved iron in the marine environment. This finding provides further insights into the Trojan Horse hypothesis, suggesting that alterophages may act as natural iron-binding ligands in the marine environment.

Bacteriophages

Trace elements in man.

It is likely that most, if not all, of the elements found to be essential in animals will be shown to be so for man, and the clinical picture produced by deficiency of the elements in the human patient will differ little from that seen in the animal, although this has been established for only five elements (I, Fe, Cu, Co and Zn). However, the link between lack of a given element in the soil and a human patient is far less direct and much more complex than that met with in the animal grazing on deficient pastures, except in isolated primitive communitis. Zn is the most protean of the trace elements and has been chosen to illustrate this in human practice. Excesses of essential elements (both trace and major) give rise to toxic effects and the importance of a proper balance especially of the transitional elements in the human diet is discussed with special reference to Cu, Zn and Fe. Certain non-essential trace elements are individual and community hazards: Cd, Pb and Hg are the principal offenders for humans. Mankind is now largely dependent on grassland products, cereals and livestock with increasing dominance of the former in human nutrition. This has reduced the bioavailability of trace elements so that study of trace metals, especially Zn and Cu, in skeletal and dental remains at human burial and occupation sites should prove useful in assessing the consequences of this striking change in dietary habits.

Biological Evolution

Application of pulse polarography with anodic stripping voltammetry to biological and toxicological analyses for lead and cadmium.

The development of polarographic techniques within the last thirty years has made possible exceptional increases in sensitivity ; thus the order of concentration studied has passed from 10-3 g ion/1. to 10-10 g ion/1. Pulse polarography with anodic stripping voltammetry is, therefore, particularly suitable for the determination of a large number of the so-called " biologically essential " and " highly toxic " metals, more often than not present in extremely low concentrations in biological samples which may be of limited volume (blood, for example). Our principal concern has been to describe and apply a method for the determination of lead and cadmium, sufficiently sensitive, precise, practical and rapid for everyday use by biologists and toxicologists. A fortiori this method is applicable in hydrology to the determination of traces of these metals in water.

Cadmium

The effect of cadmium on soluble proteins, enzymes, and essential metals of the duodenal mucosa.

In this study, it was observed that Cd administration had effects on metal distribution and enzyme activities and induced metallothionein in the soluble fraction of the duodenal mucosa. Wistar rats were given water containing 100 ppm of Cd ad libitum for 30 days. Cd treatment caused a significant increase in the mucosal weight and in the soluble protein. The existence of metallothionein was apparent and 40% of the soluble Cd was bound to the thionein. Most of the remaining Cd was bound to the larger proteins. The activities of isocitrate dehydrogenase (ICDH) and glucose-6-phosphate dehydrogenase (G6PDH) enzymes, localized in the soluble fraction, were significantly increased by Cd ingestion. The increase of Zn and the decrease of Mn and Mg were also observed in the soluble fraction of the duodenal mucosa.

Adenosine Triphosphatases

Manganese, an essential trace element for N2 fixation by Rhodospirillum rubrum and Rhodopseudomonas capsulata: role in nitrogenase regulation.

Nitrogenase (N(2)ase) from the photosynthetic bacterium Rhodospirillum rubrum can exist in two forms, an unregulated form (N(2)ase A) and a regulatory form (N(2)ase R), the latter being identified in vitro by its need for activation by a Mn(2+)-dependent N(2)ase activating system. The physiological significance of this Mn(2+)-dependent N(2)ase activating system was suggested here by observations that growth of R. rubrum and Rhodopseudomonas capsulata on N(2) gas (a condition that produces active N(2)ase R) required Mn(2+), but growth on ammonia or glutamate did not. Manganese could not be shown to be required for the biosynthesis of either nitrogenase or glutamine synthetase or for glutamine synthetase turnover, but it was required for the in vitro activation of N(2)ases from N(2) and glutamate-grown R. rubrum and R. capsulata cells. Chromatium N(2)ase, in contrast, was always fully active and did not require Mn(2+) activation, suggesting that only the purple nonsulfur bacteria are capable of controlling their N(2)ase activity by this new type of regulatory system. Although R. rubrum could not substitute Fe(2+) for Mn(2+) in the in vivo N(2) fixation process, Fe(2+) and, to a lesser extent, Co(2+) could substitute for Mn(2+) in the in vitro activation of N(2)ase. Electron paramagnetic resonance spectroscopy of buffer-washed R. rubrum chromatophores showed lines characteristic of Mn(2+). Removal of the Mn(2+)-dependent N(2)ase activating factor by a salt wash of the chromatophores removed 90% of the Mn(2+), which suggested a specific coupling of this metal to the activating factor. The data presented here all indicate that Mn(2+) plays an important physiological role in regulating the N(2) fixation process by these photosynthetic bacteria.

Ammonia

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals