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Record W2895370134 · doi:10.1021/jacs.8b08659

Sacrificial Cobalt–Carbon Bond Homolysis in Coenzyme B<sub>12</sub> as a Cofactor Conservation Strategy

2018· article· en· W2895370134 on OpenAlexaff
Gregory C. Campanello, Markus Ruetz, Greg J. Dodge, Harsha Gouda, Aditi Gupta, Umar T. Twahir, Michelle M. Killian, David Watkins, David S. Rosenblatt, Thomas C. Brunold, Kurt Warncke, Janet L. Smith, Ruma Banerjee

Bibliographic record

VenueJournal of the American Chemical Society · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPorphyrin Metabolism and Disorders
Canadian institutionsMcGill University
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesDivision of ChemistryNational Institute of General Medical SciencesNational Institutes of Health
KeywordsHomolysisChemistryCofactorCobaltOrganic chemistryRadicalEnzyme

Abstract

fetched live from OpenAlex

A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B 12 into its active cofactor forms, and to deliver it to two known B 12 -dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B 12, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B 12 product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt–carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B 12, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt–carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B 12 concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.246
Teacher spread0.238 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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

Citations30
Published2018
Admission routes1
Has abstractyes

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Same venueJournal of the American Chemical SocietySame topicPorphyrin Metabolism and DisordersFrench-language works237,207