Kinetic Studies on NADPH-Linked Aldehyde Reductase from Human Liver

Wermuth, Bendicht; Wartburg, J. P. von

doi:10.1007/978-1-4757-1419-7_20

Cited by 29 publications

(39 citation statements)

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“…PCC 7002. This suggestion is in agreement with other reports that AKRs are involved in methylglyoxal reduction in other organisms (Wermuth et al, 1977; O' Connor et al, 1999;Hinshelwood et al, 2002;Ko et al, 2005). Compared with other AKRs (Ellis, 2002), recombinant SakR1 has a high affinity for methylglyoxal and its catalytic efficiency in reducing methylglyoxal is moderately high, supporting the proposal that it plays an important role in methylglyoxal detoxification in vivo.…”

Section: Discussionsupporting

confidence: 92%

Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002

Liu

Guo

et al. 2006

Microbiology

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Aldo-keto reductases (AKRs) are a superfamily of enzymes that reduce aldehydes and ketones, and have a broad range of substrates. An AKR gene, sakR1, was identified in the cyanobacterium Synechococcus sp. PCC 7002. A mutant strain with sakR1 inactivated was sensitive to glycerol, a carbon source that can support heterotrophic growth of Synechococcus sp. PCC 7002. It was found that the sakR1 null mutant accumulated more toxic methylglyoxal than the wild-type when glycerol was added to growth medium, suggesting that SakR1 is involved in the detoxification of methylglyoxal, a highly toxic metabolite that can damage cellular macromolecules. Enzymic analysis of recombinant SakR1 protein showed that it can efficiently reduce methylglyoxal with NADPH. Based on immunoblotting, SakR1 was not upregulated at an increased cellular methylglyoxal concentration. A pH-dependent enzyme-activity profile suggested that SakR1 activity could be regulated by cellular pH in Synechococcus sp. PCC 7002. The broad substrate specificity of SakR1 implies that SakR1 could play other roles in cellular metabolism. INTRODUCTIONCyanobacteria are a diverse group of prokaryotes that carry out oxygenic photosynthesis and grow photoautotrophically. Some cyanobacteria can also grow heterotrophically in the presence of organic substrates (Rippka et al., 1979). The substrates that support heterotrophic growth of cyanobacteria include the sugars fructose and glucose. However, in the cyanobacterium Synechococcus sp. PCC 7002, glycerol is the only substrate that supports heterotrophic growth. A high concentration of exogenous glycerol is inhibitory to cyanobacterial growth, and it has been observed that glycerol-dependent growth of Synechococcus sp. PCC 7002 is only established after a period of adaptation to glycerol.Although the pathway of glycerol metabolism has not been studied in cyanobacteria in detail, it is expected that it would be the same as that of other bacteria such as Escherichia coli, since, based on cyanobacterial genome sequences, cyanobacterial cells have all the genes to encode the enzymes required for glycerol metabolism (www.kazusa.or.jp/cyanobase; J. Zhao and D. A. Bryant, unpublished data). The inhibitory effect of glycerol to cyanobacterial growth could largely be due to toxic products of glycerol metabolism. One highly toxic product of cellular glycerol metabolism is methylglyoxal (Freedberg et al., 1971), which is an electrophile and reacts with cellular macromolecules such as proteins and DNA (Ferguson et al., 1998). One of the pathways leading to methylglyoxal production in most cells is the formation of methylglyoxal from dihydroxyacetone phosphate (DHAP) enzymically or non-enzymically (Ferguson et al., 1998;Kalapos, 1999). In most cells, detoxification of methylglyoxal is through glyoxalase I-II systems (Inoue & Kimmura, 1995;Kalapos, 1999). Another important mechanism is reduction of methylglyoxal by aldo-keto reductases (AKRs), which catalyse the formation of acetol from methylglyoxal (Kalapos, 1999).AKRs are a large supe...

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Section: Discussionsupporting

confidence: 92%

Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002

Liu

Guo

et al. 2006

Microbiology

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“…The amino acid sequences of ER1, ER2, and ER3 were compared with other protein sequences in the NCBI database using the BLASTP program. The level of identity with aldehyde reductase ARI from S. salmonicolor 4) and aldehyde reductase from human 5) were 54% and 44%, respectively. We next compared the amino acid sequence of ERs with the amino acid sequences of other aldo-keto reductases by using the CLUSTALW programs.…”

Section: )mentioning

confidence: 98%

Primary Structure Analysis and Functional Expression of Erythrose Reductases from Erythritol-Producing Fungi (Trichosporonoides megachiliensisSNG-42)

Ookura

Azuma

Isshiki

et al. 2005

Bioscience, Biotechnology, and Biochemistry

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“…The enzyme prefers carboxyl-group containing negatively charged substrates, although aromatic aldehydes, steroid aldehydes, and small 3-carbon aldehydes are also reduced with high affinity (Wermuth and Monder, 1983;Branlant and Biellmann, 1980;Wermuth et al, 1977). In the reverse direction, AKR1A1 has been shown to catalyze the oxidation of proximate trans-dihydrodiols to o-quinones (Palackal et al, 2001).…”

Section: Akr1a1 -Aldehyde Reductasementioning

confidence: 99%

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski

Tipparaju

Bhatnagar

2008

Drug Metabolism Reviews

438

340

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The Aldo-Keto Reductase (AKR) superfamily comprises of several enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism and detoxification. Substrates of the family include glucose, steroids, glycosylation end products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β/α) 8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the Phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.

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Kinetic Studies on NADPH-Linked Aldehyde Reductase from Human Liver

Cited by 29 publications

References 1 publication

Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002

Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002

Primary Structure Analysis and Functional Expression of Erythrose Reductases from Erythritol-Producing Fungi (Trichosporonoides megachiliensisSNG-42)

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

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