Evidence map›Paper›PMID 41106059›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2025

Alcohol dehydrogenase 4 and aldo-keto reductase 1A1 catalyze the oxidation of 4-hydroxytolbutamide, a metabolite of tolbutamide, in the human liver.

Kazuya Shimomura, Rei Sato, Miyu Watanabe, Yuichiro Higuchi, Shotaro Uehara, Nao Yoneda, Masataka Nakano, Hiroshi Suemizu, Miki Nakajima, Tatsuki Fukami

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kazuya ShimomuraDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
Rei SatoDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
Miyu WatanabeDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
Yuichiro HiguchiLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM), Kawasaki, Japan.
Shotaro UeharaLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM), Kawasaki, Japan.
Nao YonedaLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM), Kawasaki, Japan.
Masataka NakanoDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
Hiroshi SuemizuLiver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM), Kawasaki, Japan.
Miki NakajimaDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
Tatsuki FukamiDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan. Electronic address: tatsuki@p.kanazawa-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tolbutamide is metabolized by cytochrome P450 2C9 into 4-hydroxytolbutamide (4-OH TB), which retains pharmacological activity. 4-OH TB is further oxidized to the inactive metabolite 4-carboxytolbutamide, likely via the intermediate tolbutamide aldehyde (4-CHO TB). Because the conversion of 4-OH TB to 4-CHO TB is considered the rate-limiting step, the enzyme(s) catalyzing this reaction may play a crucial role in determining drug efficacy. We aimed to identify the enzyme(s) responsible for this process in the human liver. 4-CHO TB was formed from 4-OH TB in human liver cytosol (HLC) in the presence of nicotinamide-adenine dinucleotide (NAD

Indexed as

Alcohol DehydrogenaseAldehyde ReductaseLiverTolbutamideAdultCytosolHumansMaleNADNADPOxidation-ReductionAKR1A1 protein, humanAlcohol Dehydrogenasealcohol dehydrogenase IVAldehyde ReductaseNADNADPTolbutamide4-HydroxytolbutamideADH4AKR1A1Aliphatic alcohol oxidation

Identifiers

PMID41106059
PMCPMC12799532

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.