TY - JOUR
T1 - Inhibition of deoxyhemoglobin S polymerization by glyceraldehyde
AU - Acharya, A. Seetharama
AU - Sussman, Leslie G.
AU - Jones, Wanda M.
AU - Manning, James M.
N1 - Funding Information:
This work was supported in part by NIH Grants HL-27183 (to A.S.A.) and HLl8819 (to J.M.M.).
PY - 1984/1
Y1 - 1984/1
N2 - Glyceraldehyde reacts with hemoglobin S in the intact erythrocyte to reduce the degree of polymerization, thereby inhibiting sickling of the erythrocyte. Only five of the 24 amino groups per αβ dimer react with glyceraldehyde; the adducts are present as ketoamine structures, formed by Amadori rearrangement of the initial Schiff base adducts on the protein. The reactive amino groups are the ε{lunate}-amino group of Lys-16 of the α-chain, and the α-amino group of Val-1 as well as the ε{lunate}-amino groups Lys-82, Lys-59, and Lys-120 of the β-chain. Hybrid tetramers were prepared with the modification only on Lys-16 of the α-chain or on the reactive lysine residues of the β-chain. The former derivative gels at a much higher hemoglobin concentration (23 g/dl) than either the latter derivative (16 g/dl) or unmodified deoxyhemoglobin S (15 g/dl). Thus, the modification at Lys-16 of the α-chain is a major factor in the inhibition of sickling by glyceraldehyde.
AB - Glyceraldehyde reacts with hemoglobin S in the intact erythrocyte to reduce the degree of polymerization, thereby inhibiting sickling of the erythrocyte. Only five of the 24 amino groups per αβ dimer react with glyceraldehyde; the adducts are present as ketoamine structures, formed by Amadori rearrangement of the initial Schiff base adducts on the protein. The reactive amino groups are the ε{lunate}-amino group of Lys-16 of the α-chain, and the α-amino group of Val-1 as well as the ε{lunate}-amino groups Lys-82, Lys-59, and Lys-120 of the β-chain. Hybrid tetramers were prepared with the modification only on Lys-16 of the α-chain or on the reactive lysine residues of the β-chain. The former derivative gels at a much higher hemoglobin concentration (23 g/dl) than either the latter derivative (16 g/dl) or unmodified deoxyhemoglobin S (15 g/dl). Thus, the modification at Lys-16 of the α-chain is a major factor in the inhibition of sickling by glyceraldehyde.
UR - http://www.scopus.com/inward/record.url?scp=0021291266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021291266&partnerID=8YFLogxK
U2 - 10.1016/0003-2697(84)90311-7
DO - 10.1016/0003-2697(84)90311-7
M3 - Article
C2 - 6711801
AN - SCOPUS:0021291266
SN - 0003-2697
VL - 136
SP - 101
EP - 109
JO - Analytical Biochemistry
JF - Analytical Biochemistry
IS - 1
ER -