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A Mechanistic Model of Hemoglobin Glycosylation

archives@tulane.edu / Abstract
Glucose metabolism has become of particular importance with the epidemic of diabetes rising at an exponential rate. The current clinical standard used to diagnose and monitor diabetes measures the level of glycation on the terminal valine of the β- subunit of hemoglobin (HbA1c).1,2 Current focus is limited to the extent of forming fructosamine, and although a stable product, its levels have been found to not always be a reliable index of mean blood glucose concentrations.3–5 Examination of some of the precursors to this fructosamine could be the key to understanding the discrepancies within the current HbA1c test, potentially removing the need for a systematic measurement of test result variability, the glycosylation gap (GGap).4 Using a valine derivative to mimic the terminal amino acid of hemoglobin, we were able to experimentally model this non-enzymatic reaction by reacting valinamide with glucose to produce a glucosylamine, followed by rearrangement to the more stable fructosamine. This kinetic model gives insight into the mechanistic variables involved in the formation of HbA1c and suggest that measurement of glucosylamine levels may provide a more reliable index of mean blood glucose levels. Gluconic acid is also suggested as a metabolic marker for diabetic diagnosis due to the relatively favorable oxidation of glucosylamine. Formation of gluconic acid, known to have increased concentrations in diabetics, could potentially be an alternative pathway in glucose metabolism. / 1 / Karry LeBlanc

  1. tulane:120523
Identiferoai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_120523
Date January 2020
ContributorsLeBlanc, Karry (author), Byers, Larry (Thesis advisor), School of Science & Engineering Chemistry (Degree granting institution)
PublisherTulane University
Source SetsTulane University
LanguageEnglish
Detected LanguageEnglish
TypeText
Formatelectronic, pages:  144
RightsNo embargo, Copyright is in accordance with U.S. Copyright law.

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