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Showing results 1 to 8 of 8

Journal Article

3-hydroxykynurenine is a ROS-inducing cytotoxic tryptophan metabolite that disrupts the TCA cycle

Authors : Buchanan, Jane L. (2023)

Tryptophan is an essential amino acid that is extensively characterized as a regulator of cellular function through its metabolism by indoleamine 2,3-deoxygenase (IDO) into the kynurenine pathway. However, despite decades of research on tryptophan metabolism, the metabolic regulatory roles of it and its metabolites are not well understood. To address this, we performed an activity metabolomics screen of tryptophan and most of its known metabolit...

Journal article

A generalizable protocol for expression and purification of membrane-bound bacterial phosphoglycosyl transferases in liponanoparticles

Authors : Dodge, Greg J. (2023)

Phosphoglycosyl transferases (PGTs) are among the first membrane-bound enzymes involved in the biosynthesis of bacterial glycoconjugates. Robust expression and purification protocols for an abundant subfamily of PGTs remains lacking. Recent advancements in detergent-free methods for membrane protein solubilization open the door for purification of difficult membrane proteins directly from cell membranes into native-like liponanoparticles. By leveraging autoinduction, in vivo...

Journal article

A metabolic labeling-based chemoproteomic platform unravels the physiological roles of choline metabolites

Authors : Dixit, Aditi (2023)

Choline is an essential nutrient for mammalian cells. Our understanding of the cellular functions of choline and its metabolites, independent of their roles as choline lipid metabolism intermediates, remains limited. In addition to fundamental cellular physiology, this knowledge has implications for cancer biology because elevated choline metabolite levels are a hallmark of cancer. Here, we establish the mammalian choline metabolite-interacting proteome by...

Journal Article

Homocysteine Metabolites Impair the Phf8/H4K20me1/mTOR/Autophagy Pathway by Upregulating the Expression of PHF8-targeting miR-22-3p and miR-1229-3p in Human Vascular Endothelial Cells

Authors : Jakubowski, Hieronim (2023)

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites,&#...

Journal article

Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype

Authors : Bhattacharyya, Sanchari (2021)

The relationship between sequence variation and phenotype is poorly understood. Here we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations in Dihydrofolate Reductase (DHFR). We find that partial loss of DHFR activity causes reversible filamentation despite SOS response indicative of DNA damage, in contrast to thymineless death (TLD) achieved by complete inhibition of&#...

Journal article

Pre-analytical processing of plasma and serum samples for combined proteome and metabolome analysis

Authors : Gegner, Hagen M. (2023)

Metabolomic and proteomic analyses of human plasma and serum samples harbour the power to advance our understanding of disease biology. Pre-analytical factors may contribute to variability and bias in the detection of analytes, especially when multiple labs are involved, caused by sample handling, processing time, and differing operating procedures. To better understand the impact of pre-analytical factors that are relevant to implement a unified proteomic and...

Journal article

Proteomics and metabolomics reveal an abundant α-glucosidase drives sorghum fermentability for beer brewing

Authors : Kerr, E. D. (2023)

Sorghum (Sorghum bicolor), a grass native to Africa, is a popular alternative to barley for brewing beer. The importance of sorghum to beer brewing is increasing because it is a naturally gluten-free cereal and because climate change is expected to cause a reduction in the production of barley over the coming decades. However, there are challenges associated with the use of sorghum instead of barley in beer brewing. Here,...

Journal article

Spatial distribution of metabolites in primate retina and its relevance to studies of human metabolic retinal disorders

Authors : Bonelli, Roberto (2023)

The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula. To better understand the properties of different retinal areas we conducted an untargeted...