Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 363-364
CORRESPONDENCE
An Erythroid-Specific Exon Is Present in the Human Hexokinase
Gene
 |
LETTER |
To the Editor:
Human hexokinase type I (EC 2.7.1.1) is the predominant
glucose-phosphorylating enzyme in red blood cells. By a number of
methods1 it has been proved, and is now widely accepted,
that this enzyme is largely heterogeneous and present in multiple
molecular forms. Hexokinase subtypes have similar kinetic properties
but a different age-dependent decay and a different intracellular
distribution in reticulocytes.
It is presently unknown if the multiple hexokinase subtypes reflect
posttranslational modifications or different gene products. We
previously showed that, at least in human placenta, the heterogeneity
of hexokinase type I is caused by the presence of truncate forms
arising postsynthetically.2
In the February issue of BLOOD, Murakami and Piomelli3
reported evidence for a red cell-specific hexokinase cDNA containing a
unique sequence of 60 nucleotides at the beginning of the coding
region. We have now identified this red cell-specific hexokinase
sequence in the human genome and found that it is located 3.1 kb
upstream from the somatic exon 1 (GenBank accession number AF016350).
Determination of the splice-junction by direct sequencing confirmed the
hypothesis that a true hexokinase isozyme may exist in humans, likely
as a product of an alternative splicing event. However, human
erythrocytes show a multiplicity of forms that cannot be explained only
on the bases of two alternative hexokinase isoforms.4,5
Thus, the origin of hexokinase multiplicity remains at least in part to
be determined.
Finally, we would like to note that expression of recombinant human
hexokinase type I lacking the porin-binding domain results in an enzyme
with normal kinetic and regulatory properties (Bianchi et al, submitted
for publication). Thus, in cases of hexokinase mutations
with altered enzymatic properties, the mutation must be searched for
downstream of exon 1. This exon could instead confer stability to the
enzyme by favoring binding to intracellular organelles and be
responsible for enzyme defects with accelerated in vivo hexokinase
decay.6
| |
ACKNOWLEDGMENT |
Francesca Andreoni was supported by ENEA fellowship.
Annamaria Ruzzo
Francesca Andreoni
Mauro Magnani
"G. Fornaini"
Institute of Biological Chemistry
University of Urbino
Urbino,
Italy
| |
REFERENCES |
1.
Wilson JE:
Hexokinases.
Rev Physiol Biochem Pharmacol
126:65,
1995[Medline]
[Order article via Infotrieve]
2.
Magnani M,
Serafini G,
Bianchi M,
Casabianca A,
Stocchi V:
Human hexokinase type I microheterogeneity is due to different amino-terminal sequences.
J Biol Chem
266:502,
1991[Abstract/Free Full Text]
3.
Murakami K,
Piomelli S:
Identification of the cDNA for human red blood cell-specific hexokinase isozyme.
Blood
89:762,
1997[Abstract/Free Full Text]
4.
Magnani M,
Serafini G,
Stocchi V:
Hexokinase type I multiplicity in human erythrocytes.
Biochem J
254:617,
1988[Medline]
[Order article via Infotrieve]
5.
Rifken G,
Vansen G,
Kraaijenhagen RJ,
van der Vist MJM,
Vlug AMC,
Staal GEJ:
Separation and characterization of hexokinase I subtypes from human erythrocytes.
Biochem Biophys Acta
659:292,
1981[Medline]
[Order article via Infotrieve]
6.
Magnani M,
Crinelli R,
Antonelli A,
Casabianca A,
Serafini G:
The soluble but not mitochondrially bound hexokinase is a substrate for the ATP- and ubiquitin-dependent proteolytic system.
Biochem Biophys Acta
1206:180,
1994[Medline]
[Order article via Infotrieve]
