Structural Biochemistry/Protein function/Heme group/Hemoglobin/AHSP

AHSP Prevents Excess Free Alpha-globin Chains

Because alpha chains are coded for by four loci, compared to the two that code for beta chains, excess alpha chains are produced and must be stabilized in order to keep them in solution and prevent them from precipitating out. This is achieved by the production of an alpha hemoglobin stabilizing protein (i.e.-AHSP). This protein binds to the alpha chains in the same manner that the beta chains do and creates a soluble complex. It binds to the alpha hemoglobin as it’s produced and is then displaced by the beta hemoglobin produced which forms a more favorable and stable dimer. This way there is no excess alpha hemoglobin which would accumulate and precipitate out of solution.

AHSP Assists in Tetramer Assembly

AHSP is important not only for dealing with newly synthesized excess α-globin, but also in the assembly of normal Hb tetramers. Studies now show that mice infected with mild α-Thalassemia, a condition which causes a deficit of α-globin and an excess of β-globin, still utilize AHSP. No AHSP was expected to be needed by these mice because there was no risk of excess α-globin accumulating and precipitating out, however, when the mice with no AHSP and α-Thalassemia were compared to both normal mice, and mice with α-Thalassemia and intact AHSP, they were far more anemic, showing AHSP has other roles besides stabilizing excess α-globin.

Other Functions of AHSP

Besides being an important molecular chaperone in Hb assembly, AHSP may also provide an additional selective advantage to red cells under conditions of oxidative stress induced by drugs, because of its effects on preventing α-globin denaturation and promoting renaturation. AHSP may also be useful to red cells in iron deficiency in which heme availability is limited and apo-α-globin levels are increased and help stabilize red blood cells in the presence of environmental factors that alter Hb’s critical equilibrium.

Sources

http://www.pubmedcentral.nih.gov/

Berg, Jeremy M. John L. Tymoczko. Lubert Stryer. Biochemistry Sixth Edition. W.H. Freeman and Company. New York, 2007.