Gene expression and biological significance of hexokinase in erythroid cells.
Red blood cells (RBCs) express two hexokinase (HK) isoforms, HK-I and HK-R. Both isozymes are generated from the HK-I gene by use of an alternate promoter. Gene structure and exon-intron organization of the HK-I gene have been elucidated from a sequence of three contiguous genomic clones localized at human chromosome 10. The sequence spans about 131 kb, and consists of 25 exons, which include 6 testis- and 1 erythroid-specific exons. HK-R has been shown as an erythroid-specific isozyme whose expression is turned on in the early erythroid-progenitors and is significantly induced during their differentiation. HK-R unfolds major HK activity in immature RBCs and is rapidly degraded during the maturation process. HK-I has a porin-binding domain in its N-terminus. Recent studies have shown that HK isozymes with a porin-binding domain play a role in mitochondrial integrity, suggesting that HK-I-deficient erythroid cells might be eliminated by apoptosis. It is most likely that RBCs are most labile as a result of HK-I/R deficiency since the HK-I gene but not the other isozyme genes are expressed in fetal and adult RBCs.
Murakami
Koko
K
Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Kanno
Hitoshi
H
Tancabelic
Jakica
J
Fujii
Hisaichi
H
D000743:Anemia, Hemolytic / Q000201:enzymology / Q000473:pathology; D004912:Erythrocytes / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D006593:Hexokinase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D007527:Isoenzymes; D006593:Hexokinase