Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis

Pequerul, Raquel; Vera, Javier; Gimenez-Dejoz, Joan; Coines, Joan; Porté, Sergio; Rovira, Carme; Parés, Xavier; Farrés, Jaume

doi:10.1016/j.abb.2020.108256

Cited by 27 publications

(45 citation statements)

References 58 publications

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“…ALDH enzymes are diverse in their function across all kingdoms of life, contributing to detoxification Esterbauer et al (1991), Kelson et al (1997), Choudhary et al (2005), Ho and Weiner (2005), Rodríguez-Zavala et al (2006), Marchitti et al (2007), Shin et al (2009), Jackson et al (2011), Ouyang et al (2020, biosynthesis Yoshida et al (1992), Mellema et al (2002), Kim et al (2015), Pequerul et al (2020), and non-enzymatic functions such as anti-oxidant Estey et al (2007), Lassen et al (2008), Marchitti et al (2011, Voulgaridou et al (2020), structural Piatigorsky (1998), Voulgaridou et al (2017) and regulatory mechanisms Moreb (2008), Vassalli (2019), Voulgaridou et al (2020) (Table 1). Proper function of these enzymes is essential for maintenance of cell function and survival, with prominent ALDH-linked diseases arising from mutation, catalytic knockout and structural disruption.…”

Section: Structural Perspective Of Aldehyde Dehydrogenase Related Diseasesmentioning

confidence: 99%

Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective

Shortall

Djeghader

Magner

et al. 2021

Front. Mol. Biosci.

116

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Aldehyde dehydrogenases engage in many cellular functions, however their dysfunction resulting in accumulation of their substrates can be cytotoxic. ALDHs are responsible for the NAD(P)-dependent oxidation of aldehydes to carboxylic acids, participating in detoxification, biosynthesis, antioxidant and regulatory functions. Severe diseases, including alcohol intolerance, cancer, cardiovascular and neurological diseases, were linked to dysfunctional ALDH enzymes, relating back to key enzyme structure. An in-depth understanding of the ALDH structure-function relationship and mechanism of action is key to the understanding of associated diseases. Principal structural features 1) cofactor binding domain, 2) active site and 3) oligomerization mechanism proved critical in maintaining ALDH normal activity. Emerging research based on the combination of structural, functional and biophysical studies of bacterial and eukaryotic ALDHs contributed to the appreciation of diversity within the superfamily. Herewith, we discuss these studies and provide our interpretation for a global understanding of ALDH structure and its purpose–including correct function and role in disease. Our analysis provides a synopsis of a common structure-function relationship to bridge the gap between the highly studied human ALDHs and lesser so prokaryotic models.

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Section: Structural Perspective Of Aldehyde Dehydrogenase Related Diseasesmentioning

confidence: 99%

Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective

Shortall

Djeghader

Magner

et al. 2021

Front. Mol. Biosci.

116

View full text Add to dashboard Cite

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“…The k cat / K m value for retinal (45 min −1 μM −1 ) of AKR1B10 is much higher than those (0.14–5.3 min −1 μM −1 ) of the other AKRs [ 5 , 34 ], DHRS4 [ 36 ], DHRS7 [ 37 ], and RDH13 [ 38 ], although its K m value for retinal (0.6 μM) is higher than those of RDH11, RDH12 and RDH14 (0.04–0.15 μM) [ 38 ] and DHRS3 [ 39 ]. In addition, the K m and k cat / K m values of AKR1B10 are much lower and higher, respectively, than K m (2.4–11 μM) and k cat / K m values (1.6–7.6 min −1 μM −1 ) of aldehyde dehydrogenases (ALDHs: 1A1, 1A2 and 1A3) [ 40 ], which catalyze the oxidation of retinal to retinoic acid. Thus, AKR1B10 acts as one of the enzymes that control the cellular concentration of retinal, and contributes to maintain the retinoid homeostasis in normal gastrointestinal tissues with its high-expression.…”

Section: Akr1b10 As a Multifunctional Nadph-dependent Reductasementioning

confidence: 99%

The Role of AKR1B10 in Physiology and Pathophysiology

2021

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AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.

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“…SLC22A18 regulating the IGFBP1 expression increased the supply of intracellular FFAs from TG‐rich lipid droplets 69 . ALDH1A2 and DHRSX are enzymes that cause lipid peroxidation 70,27 . ACSBG1is an acyl‐CoA synthetases that activate fatty acids to their CoA derivatives play a central role in fatty acid metabolism 71 .…”

Section: Discussionmentioning

confidence: 99%

Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1

Zhou

Zhang

Yang

et al. 2021

Clinical & Translational Med

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Background Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration‐resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. Methods We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. Results We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta‐analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1‐knockout (Ces −/− ) mice verified the important role of endogenous Ces1 in PCa. Conclusions Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa.

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Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis

Cited by 27 publications

References 58 publications

Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective

Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective

The Role of AKR1B10 in Physiology and Pathophysiology

Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1

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