S-Sulfo-Cysteine is an Endogenous Amino Acid in Neonatal Rat Brain but an Unlikely Mediator of Cysteine Neurotoxicity

Abbas, Abdul-Karim; Xia, Wanlin; Tranberg, Mattias; Wigström, Holger; Weber, Stephen G.; Sandberg, Mats

doi:10.1007/s11064-007-9441-7

Cited by 10 publications

(5 citation statements)

References 45 publications

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“…Our analysis also revealed discrete serum metabolites associated with COVID-19 that may account for some of the varying clinical outcomes in these patients. For example, metabolites that were positively associated with COVID-19 (table S3) have inflammatory [palmitoleic ( 23 ) and arachidonic acids ( 24 )] and neurological [glutamate ( 25 ) and cysteine- S -sulfate ( 26 )] roles. Metabolites that were negatively associated with COVID-19 are involved in the urea cycle and the nitric oxide (NO) synthesis pathway [proline, citrulline, and glutamine ( 27 )].…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid may underlie sex-specific immune responses to COVID-19

et al. 2021

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Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.

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Section: Discussionmentioning

confidence: 99%

Kynurenic acid may underlie sex-specific immune responses to COVID-19

et al. 2021

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“…The analysis in this study also revealed discrete serum metabolites associated with COVID-19 that may account for some of the varying clinical outcomes in these patients. For instance, metabolites that were positively associated with COVID-19 ( Extended Data Table 3 ) have inflammatory (palmitoleic 23 and arachidonic acids 24 ) and neurological (glutamate 25 and cysteine-S-sulfate 26 ) roles. Metabolites negatively associated with COVID-19, are involved in the urea cycle and nitric oxide (NO) synthesis pathway (proline, citrulline, and glutamine 27 ).…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid underlies sex-specific immune responses to COVID-19

Cai¹,

Kim

Takahashi

et al. 2020

Preprint

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Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.

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“…Elevated sulfite levels lead to progressive neurological damage [Sass et al, 2003; Zhang et al, 2004], while the contribution of other metabolites such as taurine, S‐sulfocystein, and thiosulfate to the disease progression is not yet fully understood [Abbas et al, 2008]. Usually seizures start shortly after birth and feeding difficulties remind of amino acid intolerance.…”

Section: Phenotype and Diagnosismentioning

confidence: 99%

Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2

2010

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All molybdenum‐containing enzymes other than the bacterial nitrogenase share an identical molybdenum cofactor (MoCo), which is synthesized via a conserved pathway in all organisms and therefore also is called “universal molybdenum cofactor.” In humans, four molybdoenzymes are known: aldehyde oxidase, mitochondrial amidoxime reducing component (mARC), xanthine oxidoreductase, and sulfite oxidase. Mutations in the genes encoding the biosynthetic MoCo pathway enzymes abrogate the activities of all molybdoenzymes and result in the “combined” form of MoCo deficiency, which is clinically very similar to isolated sulfite oxidase deficiency, caused by mutations in the gene for the corresponding apoenzyme. Both deficiencies are inherited as an autosomal‐recessive disease and result in progressive neurological damage and early childhood death in most cases. The majority of mutations leading to MoCo deficiency have been identified in the genes MOCS1 (type A deficiency), MOCS2 (type B deficiency), with one reported in GPHN. For type A deficiency an effective substitution therapy has been described recently. Hum Mutat 32:10–18, 2011. © 2010 Wiley‐Liss, Inc.

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S-Sulfo-Cysteine is an Endogenous Amino Acid in Neonatal Rat Brain but an Unlikely Mediator of Cysteine Neurotoxicity

Cited by 10 publications

References 45 publications

Kynurenic acid may underlie sex-specific immune responses to COVID-19

Kynurenic acid may underlie sex-specific immune responses to COVID-19

Kynurenic acid underlies sex-specific immune responses to COVID-19

Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2

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