
@article {144783,
	title = {Albumin Oxidation and Albumin Glycation Discordance During Type 2 Diabetes Therapy: Biological and Clinical Implications.},
	journal = {Metab Syndr Relat Disord},
	volume = {22},
	year = {2024},
	month = {2024 Jun},
	pages = {372-384},
	abstract = {<p>Cys34 albumin redox modifications (reversible "cysteinylation" and irreversible "di/trioxidation"), besides being just oxidative stress biomarkers, may have primary pathogenetic roles to initiate and/or aggravate cell, tissue, and vascular damage in diabetes. In an exploratory "proof-of-concept" pilot study, we examined longitudinal changes in albumin oxidation during diabetes therapy. Mass spectrometric analysis was utilized to monitor changes in human serum albumin (HSA) post-translational modifications {glycation [glycated albumin (GA)], cysteinylation [cysteinylated albumin (CA) or human non-mercaptalbumin-1; reversible], di/trioxidation (di/trioxidized albumin or human non-mercaptalbumin-2; irreversible), and truncation (truncated albumin)} during ongoing therapy. Four informative groups of subjects were evaluated [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity, and healthy controls] at baseline, and subjects with diabetes were followed for a period up to 280 days. At baseline, T2DM was associated with relatively enhanced albumin cysteinylation (CA\% total) compared with T1DM ( = 0.004), despite comparable mean hyperglycemia ( values: hemoglobin A1c = 0.09; GA = 0.09). T2DM, compared with T1DM, exhibited selectively and significantly higher elevations of all the "individual" glycated cum cysteinylated ("multimodified") albumin isoforms ( values: CysHSA+1G = 0.003; CysHSA+2G = 0.007; and CysHSA+3G = 0.001). Improvements in glycemic control and decreases in albumin glycation during diabetes therapy in T2DM were not always associated with concurrent reductions of albumin cysteinylation, and in some therapeutic situations, albumin cysteinylation worsened (glycation-cysteinylation discordance). Important differences were observed between the effects of sulfonylureas and metformin on albumin molecular modifications. T2DM was associated with higher oxidative (cysteinylation) and combined (cysteinylation plus glycation) albumin molecular modifications, which are not ameliorated by improved glucose control alone. Further studies are required to establish the clinical significance and optimal therapeutic strategies to address oxidative protein damage and resulting consequences in diabetes.</p>
},
	keywords = {Adult, Aged, Biomarkers, Blood Glucose, Case-Control Studies, Cysteine, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Glycated Serum Albumin, Glycation End Products, Advanced, Glycosylation, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Oxidation-Reduction, Oxidative Stress, Pilot Projects, Protein Processing, Post-Translational, Serum Albumin, Serum Albumin, Human},
	issn = {1557-8518},
	doi = {10.1089/met.2023.0275},
	author = {Vaishnav, Madhumati S and Kumari, Namita and Srikanta, Sathyanarayana and Simha, Vinaya and Krishnaswamy, Patnam R and Balaram, Padmanabhan and Bhat, Navakanta}
}
@article {1027,
	title = {Rise of the Helix from a Collapsed Globule during the Folding of Monellin.},
	journal = {Biochemistry},
	volume = {54},
	year = {2015},
	month = {2015 Sep 1},
	pages = {5356-65},
	abstract = {<p>Early kinetic intermediates observed during the folding of many proteins are invariably compact and appear to possess some secondary structure. Consequently, it has been difficult to understand whether compaction drives secondary structure formation or secondary structure formation facilitates compaction during folding. In this study of the folding of single-chain monellin, it is shown that a kinetic molten globule (MG) is populated at 2 ms of folding. Far-UV circular dichroism (CD) measurements show that the kinetic MG is devoid of any helical structure even under the most stabilizing folding conditions. Multisite fluorescence resonance energy transfer (FRET) measurements show that the kinetic MG is compact with different segments having contracted to different extents. It is shown that the sequence segment that goes on to form the sole helix in the native protein is fully collapsed in the kinetic MG. This segment expands to accommodate the helix as the kinetic MG folds further to the native state, while other segments of the protein contract. Helix formation starting from the kinetic MG is shown to occur in multiple kinetic steps, whether measured by far-UV CD or by FRET.</p>
},
	keywords = {Amino Acid Substitution, Circular Dichroism, Cysteine, Fluorescence Resonance Energy Transfer, Hydrophobic and Hydrophilic Interactions, Kinetics, Models, Molecular, Mutagenesis, Site-Directed, Plant Proteins, Protein Conformation, Protein Folding, Protein Stability, Protein Structure, Secondary, Spectrometry, Fluorescence},
	issn = {1520-4995},
	doi = {10.1021/acs.biochem.5b00730},
	author = {Goluguri, Rama Reddy and Udgaonkar, Jayant B}
}
