Some factors that influence the nonenzymatic glycation of peptides and polypeptides by glyceraldehyde.
The rate of reaction of glyceraldehyde with a series of peptides was found to be dependent on their amino acid composition, sequence, and chain length. The presence of a histidine near the NH2-terminal increased the rate of glycation, whereas the presence of a carboxyl group near the reaction site led to a decrease in reaction rate. In general, tripeptides reacted faster than dipeptides, and dipeptides reacted faster than amino acids. Sodium phosphate and 2,3-diphosphoglycerate enhanced the rate of reaction of glyceraldehyde with all the dipeptides tested. Sodium chloride inhibited the reaction in phosphate buffer, but not in HEPES buffer. The NH2-terminal heptapeptide from the beta-chain of human hemoglobin A (HbA), where histidine is the second residue, reacted with glyceraldehyde faster than the NH2-terminal hexapeptide from the alpha-chain. The glycation of tetrameric human Hb by glyceraldehyde was found to be dependent on the ligation state of the protein since deoxy-HbA reacted about 50% more with glyceraldehyde than did liganded HbA. The enhanced glycation of deoxy HbA was mainly attributable to the more extensive reaction at the NH2-terminal of the beta-chain. The presence of a histidine adjacent to the NH2-terminal at this site may facilitate the Amadori rearrangement. The glycation of horse Hb in which the second residue is glutamine was not increased under anaerobic conditions.
Bai
Y
Y
Rockefeller University, New York, New York 10021.
Ueno
H
H
Manning
J M
JM
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002263:Carboxyhemoglobin; D055598:Chemical Phenomena; D002621:Chemistry; D005985:Glyceraldehyde; D006031:Glycosylation; D006441:Hemoglobin A; D006736:Horses; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009842:Oligopeptides; D010455:Peptides
D000596:Amino Acids; D009842:Oligopeptides; D010455:Peptides; D005985:Glyceraldehyde; D006441:Hemoglobin A; D002263:Carboxyhemoglobin