Preferred Label : Hemoglobin Chaperone Pathway;
NCIt related terms : Hemoglobin's Chaperone;
Alternative definition : BIOCARTA: The function of hemoglobin in oxygen transport by red blood cells requires
precise assembly of a tetramer of two beta-subunits and two alpha-units. If too many
beta-subunits are present, then all tetramers of beta-subunits are formed that bind
oxygen but do not release it when needed. When alpha-subunits are in excess they form
precipitates with oxidized heme that damage red blood cells. Red blood cells require
a precise coregulation of alpha and beta subunit expression to maintain the proper
ratio of the subunits and normal red blood cell function. Generally red blood cells
express slightly more alpha than beta-subunits to avoid forming unproductive beta-tetramers
(HbH). The slight excess of alpha units are blocked from precipitation by a molecular
chaperone, AHSP, alpha-hemoglobin stabilizing protein. Expression of the AHSP gene
is coordinately activated with the globin genes and heme biosynthesis genes by the
GATA-1 gene involved in erythrocyte differentiation. AHSP blocks precipitation of
alpha-units, and promotes the formation of normal productive alpha-beta tetramers
(HbA). People with mutation or deletion of the beta-subunit gene have Beta-thalassemias
resulting from an over-abundance of alpha subunits and their precipitation. The severity
of the phenotype may depend on the AHSP genotype of these individuals and elevating
AHSP levels through gene therapy may provide a treatment strategy for beta-thalassemia.
(This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_ahspPathway;
Origin ID : C38976;
UMLS CUI : C1512401;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
