This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Maillard reaction between sugars and amines is a principal contributor to the colors, flavors, and aromas generated in baked/fried foods and to the production of advanced glycation end-products (AGEs) in physiological systems. Ribose 5-phosphate (R5P), a component of the pentose phosphate pathway in cells, has been shown to undergo the Maillard browning reaction with simple amines at rates approximately 100 times faster than most other common sugars and sugar phosphates. The potential of significant R5P glycation of cellular amines and proteins is, however, currently poorly understood. The goal of the project was to fully characterize kinetics and reaction mechanisms of the reaction of R5P with amines with particular attention towards the effect of the reaction on protein cross-linking and function. R5P (50 mM) was shown to react rapidly with simple amines/amino acids and target proteins (lysozyme, lactalbumin, ribonuclease A, histones, myoglobin) at 37 C with initial interactions noted generally within hours and browning reactions obvious generally within a day. Native gel and isoelectric focusing electrophoretic patterns suggest a rapid replacement of basic amine side chains (lysines and arginines) with negatively charged R5P groups. Modeling of the R5P/protein system vs. a simple R5P/N-acetyl lysine system illustrates an enhanced rate for the reaction with proteins. R5P was eventually removed from solution despite a greater than ten-fold molar excess over total protein amine levels, thus indicating a repeated R5P-degrading reaction coupled with subsequent regeneration of the initial amine group. 31P nuclear magnetic resonance (NMR) spectroscopy analysis of microfiltrated samples of the reaction revealed phosphate loss from the R5P nucleus with time. Protein protein cross-linking was remarkably fast with dimers being seen within 4 h for systems with highly basic proteins (i.e. histones) and within four days for more neutral proteins. The implications of this investigation strengthen a proposal that R5P could be a significant source of advanced glycation end-products (AGEs) in cellular conditions.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016462-05
Application #
7381427
Study Section
Special Emphasis Panel (ZRR1-RI-4 (02))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$81,060
Indirect Cost
Name
University of Vermont & St Agric College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Wagner, Benjamin A; Braddick, Valerie C; Batson, Christopher G et al. (2018) Effects of testosterone dose on spatial memory among castrated adult male rats. Psychoneuroendocrinology 89:120-130
Mireault, Gina C; Crockenberg, Susan C; Heilman, Keri et al. (2018) Social, cognitive, and physiological aspects of humour perception from 4 to 8 months: Two longitudinal studies. Br J Dev Psychol 36:98-109
Mireault, Gina C; Rainville, Brady S; Laughlin, Breanna (2018) Push or Carry? Pragmatic Opportunities for Language Development in Strollers vs. Backpacks. Infancy 23:616-624
Mireault, Gina C (2017) Laughing MATTERS. Sci Am Mind 28:33-37
Nock, Adam M; Wargo, Matthew J (2016) Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators. J Bacteriol 198:2503-14
Spritzer, M D; Curtis, M G; DeLoach, J P et al. (2016) Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats. Neuroscience 318:143-56
Hinkle, Karen L; Anderson, Chad C; Forkey, Blake et al. (2016) Exposure to the lampricide 3-trifluoromethyl-4-nitrophenol results in increased expression of carbohydrate transporters in Saccharomyces cerevisiae. Environ Toxicol Chem 35:1727-32
Reddy, Vasudevi; Mireault, Gina (2015) Teasing and clowning in infancy. Curr Biol 25:R20-3
Symeonides, Menelaos; Murooka, Thomas T; Bellfy, Lauren N et al. (2015) HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts. Viruses 7:6590-603
Xie, Yi; Jin, Yu; Merenick, Bethany L et al. (2015) Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition. Sci Signal 8:ra44

Showing the most recent 10 out of 178 publications