Glycated hemoglobin

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Glycated Hemoglobin is a form of hemoglobin with sugars attached to certain amino acid side chains. When blood sugar levels in an individual are high for long periods of time (hyperglycemia) as is the case for people with diabetes) when blood sugar is not managed, these sugar modifications accumulate. The so-called HbA1c test[1] is used as a measure of hyperglycemia over the past ~3 months. The time span of 3 months corresponds roughly to the average time red blood cells remain in the blood stream. When they are replenished by fresh cells, these carry hemoglobin that does not yet have the modification [2].

Structure

Hemoglobin is the protein that transports oxygen in our blood. In the structure shown in the initial view (reload), all four heme groups (☼) bind to oxygen (☼). Two amino acid side chains are covalently bound to sugar molecules (☼) in a type of modification called glycated. This happened because the protein experienced high sugar levels for a long time. The sugar is is labeled fructose, but it originated from glucose. Glucose forms a glycosidic bond with the nitrogen atom of the sidechain of lysine. Then, it dehydrates to a Schiff base and undergoes Amadori rearrangement[3] (a shift in the double bond) to fructose. In hemoglobin from patients with untreated diabetes, the modifications include glucose linked to the amino terminal groups of the alpha and beta chains as well as modification of lysine side chains by glucose. The HbA1c test [4]specifically tests for the modification of the amino terminus of the beta chain (not modified in this structure).


Glycated hemoglobin (PDB ID 5hy8)

Drag the structure with the mouse to rotate

References

  1. Yonehara S, Inamura N, Fukuda M, Sugiyama K. Use of fructosyl peptide oxidase for HbA1c assay. J Diabetes Sci Technol. 2015 Mar;9(2):200-5. doi: 10.1177/1932296815569573. Epub , 2015 Jan 28. PMID:25633966 doi:http://dx.doi.org/10.1177/1932296815569573
  2. https://pdb101.rcsb.org/global-health/diabetes-mellitus/monitoring/diagnosis?more=y
  3. https://en.wikipedia.org/wiki/Amadori_rearrangement
  4. https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/GHB_E_met_Tosoh_22_Plus.pdf

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