d-amino Acids in Health and Disease: A Focus on Cancer

Bastings, Jacco J.A.J.; Eijk, Hans M. van; Damink, Steven W. M. Olde; Rensen, Sander S.

doi:10.3390/nu11092205

Cited by 123 publications

(86 citation statements)

References 168 publications

(208 reference statements)

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“…It is attractive to consider these D-amino acids as candidate biomarkers for LC. However, only D-serine and D-aspartate are considered human tissue-derived, while the rest most likely arise from microbial sources, either in the diet or from the gut microbiota [130]. This may be further evidence of gut microbiota-liver cross-talk in liver disease.…”

Section: Fibrosis and Cirrhosismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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Section: Fibrosis and Cirrhosismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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“…Among amino acids, d-amino acids were long considered to be non-functional and to occur rarely in Nature. However, increasing evidence suggests that d-amino acids are present not only in microorganisms [189,190] and plants [191], but also in mammals in a considerable amount, exerting important roles related to mental health and age-related disorders including cancer [189,[192][193][194][195][196].…”

Section: Future Perspectivesmentioning

confidence: 99%

L-Glucose: Another Path to Cancer Cells

Ono

Takigawa

Yamada

2020

Cancers

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Cancerous tumors comprise cells showing metabolic heterogeneity. Among numerous efforts to understand this property, little attention has been paid to the possibility that cancer cells take up and utilize otherwise unusable substrates as fuel. Here we discuss this issue by focusing on l-glucose, the mirror image isomer of naturally occurring d-glucose; l-glucose is an unmetabolizable sugar except in some bacteria. By combining relatively small fluorophores with l-glucose, we generated fluorescence-emitting l-glucose tracers (fLGs). To our surprise, 2-NBDLG, one of these fLGs, which we thought to be merely a control substrate for the fluorescent d-glucose tracer 2-NBDG, was specifically taken up into tumor cell aggregates (spheroids) that exhibited nuclear heterogeneity, a major cytological feature of malignancy in cancer diagnosis. Changes in mitochondrial activity were also associated with the spheroids taking up fLG. To better understand these phenomena, we review here the Warburg effect as well as key studies regarding glucose uptake. We also discuss tumor heterogeneity involving aberrant uptake of glucose and mitochondrial changes based on the data obtained by fLG. We then consider the use of fLGs as novel markers for visualization and characterization of malignant tumor cells.

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“…Derived from microorganisms or l-d racemization, d-amino acids are a pool of l-isomers that are necessary for protein synthesis and antagonists for l-isomers at biological sites. Bacterial pathogens and immune activation may cause an imbalance of d-amino acid concentrations [154]. D-TRP can be usable to promote growth in a TRP-deficient diet, and d-TRP and l-TRP were found to be equally effective in the growth of rats.…”

Section: Amino Acid Oxidase and D-amino Acidsmentioning

confidence: 99%

Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism

2020

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Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potentially upregulating multiple feedback loops of AD pathogenesis. Memantine is an N-methyl-D-aspartate glutamatergic receptor (NMDAR) antagonist, which belongs to one of only two classes of medications approved for clinical use, but other NMDAR modulators have been explored so far in vain. An endogenous KYN pathway metabolite, kynurenic acid (KYNA), likewise inhibits the excitotoxic NMDAR. Besides its anti-excitotoxicity, KYNA is a multitarget compound that triggers anti-inflammatory and antioxidant activities. Modifying the KYNA level is a potential multitarget strategy to normalize the disturbed KYN pathway and thus to alleviate juxtaposing AD pathogeneses. In this review, the maintenance of KYN metabolism by modifying the level of KYNA is proposed and discussed in search for a novel lead compound against the progression of dementia.

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d-amino Acids in Health and Disease: A Focus on Cancer

Cited by 123 publications

References 168 publications

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

L-Glucose: Another Path to Cancer Cells

Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism

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