1,5-Anhydro-D-fructose (AF), a metabolite of the anhydrofructose pathway of glycogen metabolism, has recently been shown to react with intracellular proteins and form advanced glycation end-products. The reactive AF is metabolized to non-reactive 1,5-anhydro-D-glucitol by AF reductase in animal tissues and human cells. Pig and mouse AF reductases were characterized, but primate AF reductase remains unknown. Here, we examined the AF-reducing activity of eleven primate NADPH-dependent reductases with broad substrate specificity for carbonyl compounds. AF was reduced by monkey dimeric dihydrodiol dehydrogenase (DHDH), human aldehyde reductase (AKR1A1) and human dicarbonyl/L-xylulose reductase (DCXR). DHDH showed the lowest K (21 μM) for AF, and its k/K value (1208 smM) was much higher than those of AKR1A1 (1.3 smM), DCXR (1.1 smM) and the pig and mouse AF reductases. AF is a novel substrate with higher affinity and catalytic efficiency than known substrates of DHDH. Docking simulation study suggested that Lys156 in the substrate-binding site of DHDH contributes to the high affinity for AF. Gene database searches identified DHDH homologues (with >95% amino acid sequence identity) in humans and apes. Thus, DHDH acts as an efficient AF reductase in primates.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2020.03.176 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, -Dihydroxylation and Epoxidation.
Int J Mol Sci
January 2022
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR CNRS 8601, Université de Paris, 45 rue des Saints-Pères, 75006 Paris, France.
Article Synopsis
- Enzymatic oxidations of thiophenes play a crucial role in biodesulfurization processes and the metabolism of thiophene-containing pharmaceuticals.
- Reactive metabolites formed during oxidative reactions, such as sulfoxides and epoxides, can be unstable, which poses challenges in studying their properties and behaviors.
- The success of predicting the structures and configurations of chiral metabolites from thiophene oxidation relies on the specific substrate, the selected type of oxygenase, and results from molecular docking studies.
Dimeric dihydrodiol dehydrogenase is an efficient primate 1,5-anhydro-D-fructose reductase.
Biochem Biophys Res Commun
June 2020
Gifu Pharmaceutical University, Gifu, 501-1196, Japan. Electronic address:
1,5-Anhydro-D-fructose (AF), a metabolite of the anhydrofructose pathway of glycogen metabolism, has recently been shown to react with intracellular proteins and form advanced glycation end-products. The reactive AF is metabolized to non-reactive 1,5-anhydro-D-glucitol by AF reductase in animal tissues and human cells. Pig and mouse AF reductases were characterized, but primate AF reductase remains unknown.
View Article and Find Full Text PDFCharacterisation of the cellular and proteomic response of Galleria mellonella larvae to the development of invasive aspergillosis.
BMC Microbiol
June 2018
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
Background: Galleria mellonella larvae were infected with conidia of Aspergillus fumigatus and the cellular and humoral immune responses of larvae to the pathogen were characterized as invasive aspergillosis developed.
Results: At 2 h post-infection there was an increase in hemocyte density to 7.43 ± 0.
Effects of Black Raspberry Extract and Berry Compounds on Repair of DNA Damage and Mutagenesis Induced by Chemical and Physical Agents in Human Oral Leukoplakia and Rat Oral Fibroblasts.
Chem Res Toxicol
December 2017
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of systems, with most studies focusing on progression. Previously we reported that an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo-[a,l]-pyrene dihydrodiol (DBP-diol)-induced DNA adducts and inhibited DBP-diol and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast cell line, suggesting a role for BRB in the inhibition of initiation of carcinogenesis. Here we extend this work to protection by BE against DNA adduct formation induced by dibenzo-[a,l]-pyrene (DBP) in a human oral leukoplakia cell line (MSK) and to a second carcinogen, UV light.
View Article and Find Full Text PDFCheckpoint protein Rad9 plays an important role in nucleotide excision repair.
DNA Repair (Amst)
April 2013
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Rad9, an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity, has been shown to play important roles in homologous recombination repair, base excision repair and mismatch repair. However, whether Rad9 has an impact on nucleotide excision repair remains unknown. Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV-derived photoproduct 6-4PP (6,4 pyrimidine-pyrimidone) and the BPDE (anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide)-DNA adducts in mammalian cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!