Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes

Phospholipid oxidation generates several bioactive aldehydes that remain esterified to the glycerol backbone (‘core’ aldehydes). These aldehydes induce endothelial cells to produce monocyte chemotactic factors and enhance monocyte–endothelium adhesion. They also serve as ligands of scavenger receptors for the uptake of oxidized lipoproteins or apoptotic cells. The biochemical pathways involved in phospholipid aldehyde metabolism, however, remain largely unknown. In the present study, we have examined the efficacy of the three mammalian AKR (aldo-keto reductase) families in catalysing the reduction of phospholipid aldehydes. The model phospholipid aldehyde POVPC [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine] was efficiently reduced by members of the AKR1, but not by the AKR6 or the ARK7 family. In the AKR1 family, POVPC reductase activity was limited to AKR1A and B. No significant activity was observed with AKR1C enzymes. Among the active proteins, human AR (aldose reductase) (AKR1B1) showed the highest catalytic activity. The catalytic efficiency of human small intestinal AR (AKR1B10) was comparable with the murine AKR1B proteins 1B3 and 1B8. Among the murine proteins AKR1A4 and AKR1B7 showed appreciably lower catalytic activity as compared with 1B3 and 1B8. The human AKRs, 1B1 and 1B10, and the murine proteins, 1B3 and 1B8, also reduced C-7 and C-9 sn-2 aldehydes as well as POVPE [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphoethanolamine]. AKR1A4, B1, B7 and B8 catalysed the reduction of aldehydes generated in oxidized C16:0-20:4 phosphatidylcholine with acyl, plasmenyl or alkyl linkage at the sn-1 position or C16:0-20:4 phosphatidylglycerol or phosphatidic acid. AKR1B1 displayed the highest activity with phosphatidic acids; AKR1A4 was more efficient with long-chain aldehydes such as 5-hydroxy-8-oxo-6-octenoyl derivatives, whereas AKR1B8 preferred phosphatidylglycerol. These results suggest that proteins of the AKR1A and B families are efficient phospholipid aldehyde reductases, with non-overlapping substrate specificity, and may be involved in tissue-specific metabolism of endogenous or dietary phospholipid aldehydes.

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Mutation of threonine-241 to proline eliminates autocatalytic modification of human carbonyl reductase

Biochemical Journal ◽

10.1042/bj3500089 ◽

2000 ◽

Vol 350 (1) ◽

pp. 89-92 ◽

Cited By ~ 3

Author(s):

Michel A. SCIOTTI ◽

Shizuo NAKAJIN ◽

Bendicht WERMUTH ◽

Michael E. BAKER

Keyword(s):

Catalytic Activity ◽

Local Structure ◽

Reductase Activity ◽

Catalytic Efficiency ◽

Local Environment ◽

Carbonyl Reductase ◽

Unusual Property ◽

Wild Type ◽

Autocatalytic Process ◽

Oxocarboxylic Acids

Carbonyl reductase catalyses the reduction of steroids, prostaglandins and a variety of xenobiotics. An unusual property of human and rat carbonyl reductases is that they undergo modification at lysine-239 by an autocatalytic process involving 2-oxocarboxylic acids, such as pyruvate and 2-oxoglutarate. Comparison of human carbonyl reductase with the pig enzyme, which does not undergo autocatalytic modification, identified three sites, alanine-236, threonine-241 and glutamic acid-246, on human carbonyl reductase that could be important in the reaction of lysine-239 with 2-oxocarboxylic acids. Mutagenesis experiments show that replacement of threonine-241 with proline (T241P) in human carbonyl reductase eliminates the formation of carboxyethyl-lysine-239. In contrast, the T241A mutant has autocatalytic activity similar to wild-type carbonyl reductase. The T241P mutant retains catalytic activity towards menadione, although with one-fifth the catalytic efficiency of wild-type carbonyl reductase. Replacement of threonine-241 with proline is likely to disrupt the local structure near lysine-239. We propose that integrity of this local environment is essential for chemical modification of lysine-239, but not absolutely required for carbonyl reductase activity.

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Mitochondrial Thioredoxin-Glutathione Reductase from LarvalTaenia crassiceps(Cysticerci)

Journal of Parasitology Research ◽

10.1155/2010/719856 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Alberto Guevara-Flores ◽

Irene P. del Arenal ◽

Guillermo Mendoza-Hernández ◽

Juan Pablo Pardo ◽

Oscar Flores-Herrera ◽

...

Keyword(s):

Glutathione Reductase ◽

Reductase Activity ◽

Catalytic Efficiency ◽

Dependent Manner ◽

Exchange Reactions ◽

Disulfide Exchange ◽

Oxidative Inactivation ◽

Disulfide Reductase ◽

Thioredoxin Peroxidase ◽

Thioredoxin Glutathione Reductase

Mitochondrial thioredoxin-glutathione reductase was purified from larvalTaenia crassiceps(cysticerci). The preparation showed NADPH-dependent reductase activity with either thioredoxin or GSSG, and was able to perform thiol/disulfide exchange reactions. At25∘Cspecific activities were437 ± 27mU mg-1and840 ± 49mU mg-1with thioredoxin and GSSG, respectively. ApparentKmvalues were0.87 ± 0.04 μM,41 ± 6 μM and19 ± 10 μM for thioredoxin, GSSG and NADPH, respectively. Thioredoxin from eukaryotic sources was accepted as substrate. The enzyme reduced H2O2in a NADPH-dependent manner, although with low catalytic efficiency. In the presence of thioredoxin, mitochondrial TGR showed a thioredoxin peroxidase-like activity. All disulfide reductase activities were inhibited by auranofin, suggesting mTGR is dependent on selenocysteine. The reductase activity with GSSG showed a higher dependence on temperature as compared with the DTNB reductase activity. The variation of the GSSG- and DTNB reductase activities on pH was dependent on the disulfide substrate. Like the cytosolic isoform, mTGR showed a hysteretic kinetic behavior at moderate or high GSSG concentrations, but it was less sensitive to calcium. The enzyme was able to protect glutamine synthetase from oxidative inactivation, suggesting that mTGR is competent to contend with oxidative stress.

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Promoting inherent catalytic activity and stability of TiO2 supported Pt single-atoms at CeOx-TiO2 interfaces

Journal of Materials Chemistry A ◽

10.1039/d1ta08059h ◽

2021 ◽

Author(s):

Mi Yoo ◽

Eunji Kang ◽

Hyuk Choi ◽

Hyunwoo Ha ◽

Han Seul Choi ◽

...

Keyword(s):

Catalytic Activity ◽

Catalytic Efficiency ◽

Reaction Centers ◽

Next Generation ◽

Single Atoms ◽

General Concern

Single-atoms Single-atoms (SAs) with atomically coordinated reaction centers are considered the next generation catalyst that can reveal exceptional catalytic efficiency. However, the general concern about thermodynamic vulnerabilities of the SAs...

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Deacetoxycephalosporin C synthase isozymes exhibit diverse catalytic activity and substrate specificity

FEMS Microbiology Letters ◽

10.1111/j.1574-6968.2003.tb11525.x ◽

2003 ◽

Vol 218 (2) ◽

pp. 251-257 ◽

Cited By ~ 4

Author(s):

Hong Soon Chin ◽

Janet Sim ◽

Keng Ing Seah ◽

Tiow Suan Sim

Keyword(s):

Catalytic Activity ◽

Substrate Specificity

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PHOTO-CATALYTIC ACTIVITY AND PHOTO-ABSORPTION OF PLASMA-SPRAYED NANO-STRUCTURED TiO2 COATINGS

International Journal of Modern Physics B ◽

10.1142/s021797921005483x ◽

2010 ◽

Vol 24 (31) ◽

pp. 6115-6127 ◽

Cited By ~ 1

Author(s):

MARYAMOSSADAT BOZORGTABAR ◽

MEHDI SALEHI ◽

MOHAMMADREZA RAHIMIPOUR ◽

MOHAMMADREZA JAFARPOUR

Keyword(s):

Catalytic Activity ◽

Flow Rate ◽

Test Chamber ◽

Catalytic Efficiency ◽

Surface Characteristics ◽

Catalytic Performance ◽

Atmospheric Plasma ◽

Argon Flow Rate ◽

Photo Catalytic Activity ◽

Argon Flow

Titanium dioxide coatings were deposited by utilizing atmospheric plasma-spraying system. The agglomerated P25/20 nano-powder and different spraying parameters (e.g., Argon flow rate and spray distance) were used to determine their influences on the microstructure, crystalline structure, photo-absorption, and photo-catalytic performance of the coatings. The microstructure and phases of as-sprayed TiO 2 coatings were characterized by scanning electron microscope SEM and X-ray diffraction, respectively. Surface characteristics were investigated by Fourier Transform Infrared. Photo-catalytic efficiency of the elaborated samples was also determined in an environmental test chamber set-up and evaluated from the conversion rate of ethanol. The photo-absorption was determined by UV–Vis spectrophotometer. The as-sprayed TiO2 coating was photo-catalytically reactive for the degradation of ethanol. The photo-catalytic activity was influenced by spray conditions. It is found that the photo-catalytic activity is significantly influenced by anatase content, surface area, and surface state. The results showed that the argon flow rate has an influence on the microstructure, anatase content, and photo-catalytic activity of the TiO 2 coatings.

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Identification of Amino Acid Residues of the Retroviral Aspartic Proteinases Important for Substrate Specificity and Catalytic Efficiency

Aspartic Proteinases - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-1871-6_52 ◽

1995 ◽

pp. 399-406 ◽

Cited By ~ 1

Author(s):

C. E. Cameron ◽

H. Burstein ◽

D. Bizub-Bender ◽

T. Ridky ◽

I. T. Weber ◽

...

Keyword(s):

Amino Acid ◽

Substrate Specificity ◽

Catalytic Efficiency ◽

Amino Acid Residues ◽

Aspartic Proteinases

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A new dopachrome-rearranging enzyme from the ejected ink of the cuttlefish Sepia officinalis.

Biochemical Journal ◽

10.1042/bj2990839 ◽

1994 ◽

Vol 299 (3) ◽

pp. 839-844 ◽

Cited By ~ 26

Author(s):

A Palumbo ◽

M d'Ischia ◽

G Misuraca ◽

L De Martino ◽

G Prota

Keyword(s):

Catalytic Activity ◽

Methyl Ester ◽

Substrate Specificity ◽

Molecular Mass ◽

Significant Inhibition ◽

Single Band ◽

Pigment Cells ◽

Sepia Officinalis ◽

High Substrate ◽

Sds Page

A melanogenic enzyme catalysing the rearrangement of dopachrome has been identified in the ejected ink of the cuttlefish Sepia officinalis. This enzyme occurs as a heat-labile protein which co-migrates with tyrosinase under a variety of chromatographic and electrophoretic conditions. On SDS/PAGE it shows like a single band with an approx. molecular mass of 85 kDa. The enzyme possesses high substrate specificity, acting on L-dopachrome (Km = 1 mM at pH 6.8) and on L-alpha-methyl-dopachrome, but not on D-dopachrome, L-dopachrome methyl ester, dopaminochrome and adrenochrome. Significant inhibition of the catalytic activity was observed with tropolone and L-mimosine. H.p.1.c. analysis of the enzyme-catalysed rearrangement of L-dopachrome revealed the quantitative formation of the decarboxylated product, 5,6-dihydroxyindole. These results point to marked differences between melanogenesis in cephalopod pigment cells and in melanocytes, which may have important implications in relation to the use of sepiomelanin as a model for studies of mammalian melanins.

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Aldehyde reductase is a major protein associated with 3-deoxyglucosone reductase activity in rat, pig and human livers

Biochemical Journal ◽

10.1042/bj2790903 ◽

1991 ◽

Vol 279 (3) ◽

pp. 903-906 ◽

Cited By ~ 39

Author(s):

T Kanazu ◽

M Shinoda ◽

T Nakayama ◽

Y Deyashiki ◽

A Hara ◽

...

Keyword(s):

Rat Liver ◽

Reductase Activity ◽

Catalytic Efficiency ◽

Major Protein ◽

Aldehyde Reductase ◽

Reductase Inhibitors ◽

Major Species ◽

Human Livers

3-Deoxyglucosone reductase activity in the extracts of rat, pig and human livers was potently inhibited by aldehyde reductase inhibitors. The major species of 3-deoxyglucosone reductase purified from human and pig livers were biochemically and immunochemically identical with aldehyde reductase. The two enzymes and rat liver aldehyde reductase exhibited higher catalytic efficiency for 3-deoxyglucosone than for D-glucuronate, a representative substrate of aldehyde reductase.

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Synthesis of 1,2-Diamine Bifunctional Catalysts for the Direct Aldol Reaction Through Probing the Remote Amide Hydrogen

Current Organocatalysis ◽

10.2174/2213337206666190301155247 ◽

2019 ◽

Vol 6 (2) ◽

pp. 171-176

Author(s):

Rajasekhar Dodda ◽

Sampak Samanta ◽

Matthew Su ◽

John Cong-Gui Zhao

Keyword(s):

Hydrogen Bonding ◽

Catalytic Activity ◽

Aldol Reaction ◽

Catalytic Efficiency ◽

Aldol Reactions ◽

Catalyst Loading ◽

Bifunctional Catalysts ◽

Amide Hydrogen ◽

Highly Efficient ◽

Direct Aldol Reaction

Background: While proline can catalyze the asymmetric direct aldol reactions, its catalytic activity and catalyst turnover are both low. To improve the catalytic efficiency, many prolinebased organocatalysts have been developed. In this regard, prolinamide-based bifunctional catalysts have been demonstrated by us and others to be highly efficient catalysts for the direct aldol reactions. Results: Using the β-acetamido- and β-tosylamidoprolinamide catalysts, the highly enantio- and diastereoselective direct aldol reactions between enolizable ketones and aldehydes were achieved (up to >99% ee, 98:2 dr). A low catalyst loading of only 2-5 mol % of the β-tosylamidoprolinamide catalyst was needed to obtain the desired aldol products in good to high yields and high stereoselectivities. Methods: By carefully adjusting the hydrogen bonding ability of the remote β-amide hydrogen of the 1,2-diamine-based prolinamide bifunctional catalysts, the catalytic activity and the asymmetric induction of these catalysts were significantly improved for the direct aldol reaction between aldehydes and enolizable ketones. Conclusion: Some highly efficient 1,2-diamine-based bifunctional prolinamide catalysts have been developed through probing the remote β-amide hydrogen for its hydrogen bonding capability. These catalysts are easy to synthesize and high enantioselectivities may be achieved at very low catalyst loadings.

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