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Cadmium: Biomolecular Interactions

2023· other· en· W4367319115 on OpenAlexaff
Douglas M. Templeton

Bibliographic record

VenueEncyclopedia of Inorganic and Bioinorganic Chemistry · 2023
Typeother
Languageen
FieldNursing
TopicTrace Elements in Health
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsCadmiumChemistryIonic radiusCytosolBiophysicsMetallothioneinBiochemistryIonBiology

Abstract

fetched live from OpenAlex

Abstract Cadmium has no known function in higher organisms, which evolved in an essentially cadmium‐free environment until the last several hundred years of industrial activity. Thus, cadmium's interactions with biological molecules are not selected by evolution but are determined fortuitously by its inorganic chemistry. Under physiological conditions, cadmium exists exclusively in the Cd 2+ ionic state, and its biomolecular interactions are dominated by two, at first sight contradictory, principles. On the one hand, Cd 2+ is a Group 12 “soft” ion, and as such shows preferential interaction with thiols and other soft ligands. On the other hand, its ionic radius is a close match to the “hard” ion Ca 2+ , and it fits by mimicry into many oxygen‐rich Ca 2+ ‐binding sites. Both aspects of Cd 2+ chemistry are covered in this article. General effects of Cd 2+ on cellular Ca 2+ levels have implications for multiple signaling pathways. Interactions of Cd 2+ with Ca 2+ binding sites in specific proteins are also of consequence. Together, these aspects of Cd 2+ biology have consequences for cell survival and proliferation, and for mechanisms of cell death. A special class of Cd 2+ ‐sequestering proteins, the thiol‐rich metallothioneins, buffer cytosolic levels of Cd 2+ , and also serve as a strong link between it and the essential Zn 2+ ion; displacement of Zn 2+ from important binding sites, not only in metallothioneins and related proteins, but also in Zn 2+ ‐binding loops (“zinc fingers”) in various transcription factors is another important theme in the biological chemistry (and toxicology) of Cd 2+ . Cellular thiols are involved as both protective antioxidants against reactive oxygen species and as signaling sensors of cellular redox status. Cadmium interacts with many of these sensing and defensive pathways. The antioxidant glutathione is a crucial player in redox biology, and Cd 2+ exerts some of its biological effects by influencing levels of protein glutathione adducts. It also interacts with proteins involved in sensing cellular oxygen levels, such as Nrf2 and the hypoxia‐inducible factor 1. The ability of Cd 2+ to act both as a Ca 2+ mimic and a thiol group poison also allows it to interact with a wide range of other proteins. In addition to proteins involved in signaling and cell death pathways, these include interactions with cell membrane transport proteins, DNA repair enzymes, and the structural components of the cytoskeleton, all with profound biological consequences. Cadmium (as the Cd 2+ ion) has truly pleiotropic, and generally adverse, effects on cells that are understood by the inorganic chemistry of its interactions with biological ligands.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Other · Consensus signal: Other
Teacher disagreement score0.045
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.262
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreOther

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2023
Admission routes1
Has abstractyes

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