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dc.contributor.authorVan der Sluis, Rencia
dc.date.accessioned2018-06-26T06:47:19Z
dc.date.available2018-06-26T06:47:19Z
dc.date.issued2018
dc.identifier.citationVan der Sluis, R. 2018. Analyses of the genetic diversity and protein expression variation of the acyl: CoA medium-chain ligases, ACSM2A and ACSM2B. Molecular genetics and genomics, 293(5):1279-1292. [https://doi.org/10.1007/s00438-018-1460-3]en_US
dc.identifier.issn1617-4615
dc.identifier.issn1617-4623 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/28082
dc.identifier.urihttps://doi.org/10.1007/s00438-018-1460-3
dc.identifier.urihttps://link.springer.com/article/10.1007/s00438-018-1460-3
dc.description.abstractBenzoate (found in milk and widely used as preservative), salicylate (present in fruits and the active component of aspirin), dietary polyphenols produced by gut microbiota, metabolites from organic acidemias, and medium-chain fatty acids (MCFAs) are all metabolised/detoxified by the glycine conjugation pathway. Xenobiotics are first activated to an acyl-CoA by the mitochondrial xenobiotic/medium-chain fatty acid: CoA ligases (ACSMs) and subsequently conjugated to glycine by glycine N-acyltransferase (GLYAT). The MCFAs are activated to acyl-CoA by the ACSMs before entering mitochondrial β-oxidation. This two-step enzymatic pathway has, however, not been thoroughly investigated and the biggest gap in the literature remains the fact that studies continuously characterise the pathway as a one-step reaction. There are no studies available on the interaction/competition of the various substrates involved in the pathway, whilst very little research has been done on the ACSM ligases. To identify variants/haplotypes that should be characterised in future detoxification association studies, this study assessed the naturally observed sequence diversity and protein expression variation of ACSM2A and ACSM2B. The allelic variation, haplotype diversity, Tajima’s D values, and phylogenetic analyses indicated that ACSM2A and ACSM2B are highly conserved. This confirmed an earlier hypothesis that the glycine conjugation pathway is highly conserved and essential for life as it maintains the CoA and glycine homeostasis in the liver mitochondria. The protein expression analyses showed that ACSM2A is the predominant transcript in liver. Future studies should investigate the effect of the variants identified in this study on the substrate specificity of these proteinsen_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.subjectXenobiotic/medium-chain fatty acid: CoA ligasesen_US
dc.subjectACSM2Aen_US
dc.subjectACSM2Ben_US
dc.subjectBenzoateen_US
dc.subjectSalicylateen_US
dc.subjectMedium-chain fatty acidsen_US
dc.subjectGlycine conjugationen_US
dc.titleAnalyses of the genetic diversity and protein expression variation of the acyl: CoA medium-chain ligases, ACSM2A and ACSM2Ben_US
dc.typeArticleen_US
dc.contributor.researchID21224919 - Van der Sluis, Rencia


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