Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. We report three patients from two unrelated families of Czech and Slovak origin with macrocytic hemolytic anemia due to GPI deficiency. The first patient had 15% of residual GPI activity resulting from two new heterozygous missense mutations c.478T>C and c.1414C>T leading to substitutions p.(Ser160Pro) and p.(Arg472Cys). Two other patients (siblings) inherited the same c.1414C>T p.(Arg472Cys) mutation in a homozygous constitution and lost approximately 89% of their GPI activity. Erythroid hyperplasia with dysplastic features was observed in the bone marrow of all three patients. Low hepcidin/ferritin ratio and elevated soluble transferrin receptor detected in our GPI-deficient patients suggest disturbed balance between erythropoiesis and iron metabolism contributing to iron overload.

• Klíčová slova
• Dysplastic erythropoiesis, Glucose-6-phosphate isomerase deficiency, Hemolytic anemia, Hepcidin to ferritin ratio, Iron loading, Soluble transferrin receptor,
• MeSH
• alely MeSH
• biologické markery MeSH
• biopsie MeSH
• dítě MeSH
• erytrocytární znaky MeSH
• erytroidní buňky metabolismus   MeSH
• erytropoéza genetika   MeSH
• genotyp MeSH
• glukosa-6-fosfátisomerasa chemie   genetika   MeSH
• hemolytická nesférocytická kongenitální anemie krev   diagnóza   genetika   MeSH
• hepcidiny krev   MeSH
• konformace proteinů MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• molekulární modely MeSH
• mutace * MeSH
• regulace genové exprese MeSH
• sekvenční analýza DNA MeSH
• substituce aminokyselin * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• železo metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• glukosa-6-fosfátisomerasa MeSH
• hepcidiny MeSH
• železo MeSH

Phosphoglucose isomerase (PGI) catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. It is involved in glycolysis and in the regeneration of glucose-6-P molecules in the oxidative pentose phosphate pathway (OPPP). In chloroplasts of illuminated mesophyll cells PGI also connects the Calvin-Benson cycle with the starch biosynthetic pathway. In this work we isolated pgi1-3, a mutant totally lacking pPGI activity as a consequence of aberrant intron splicing of the pPGI encoding gene, PGI1. Starch content in pgi1-3 source leaves was ca. 10-15% of that of wild type (WT) leaves, which was similar to that of leaves of pgi1-2, a T-DNA insertion pPGI null mutant. Starch deficiency of pgi1 leaves could be reverted by the introduction of a sex1 null mutation impeding β-amylolytic starch breakdown. Although previous studies showed that starch granules of pgi1-2 leaves are restricted to both bundle sheath cells adjacent to the mesophyll and stomata guard cells, microscopy analyses carried out in this work revealed the presence of starch granules in the chloroplasts of pgi1-2 and pgi1-3 mesophyll cells. RT-PCR analyses showed high expression levels of plastidic and extra-plastidic β-amylase encoding genes in pgi1 leaves, which was accompanied by increased β-amylase activity. Both pgi1-2 and pgi1-3 mutants displayed slow growth and reduced photosynthetic capacity phenotypes even under continuous light conditions. Metabolic analyses revealed that the adenylate energy charge and the NAD(P)H/NAD(P) ratios in pgi1 leaves were lower than those of WT leaves. These analyses also revealed that the content of plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP)-pathway derived cytokinins (CKs) in pgi1 leaves were exceedingly lower than in WT leaves. Noteworthy, exogenous application of CKs largely reverted the low starch content phenotype of pgi1 leaves. The overall data show that pPGI is an important determinant of photosynthesis, energy status, growth and starch accumulation in mesophyll cells likely as a consequence of its involvement in the production of OPPP/glycolysis intermediates necessary for the synthesis of plastidic MEP-pathway derived hormones such as CKs.

• MeSH
• alely MeSH
• Arabidopsis genetika   metabolismus   MeSH
• cukerné fosfáty metabolismus   MeSH
• cytokininy metabolismus   MeSH
• erythritol analogy a deriváty   metabolismus   MeSH
• fenotyp MeSH
• fotosyntéza * MeSH
• genetické lokusy MeSH
• glukosa-6-fosfátisomerasa chemie   genetika   metabolismus   MeSH
• listy rostlin metabolismus   MeSH
• metabolické sítě a dráhy MeSH
• mezofylové buňky metabolismus   MeSH
• mutace MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• škrob metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-C-methylerythritol 4-phosphate MeSH Prohlížeč
• cukerné fosfáty MeSH
• cytokininy MeSH
• erythritol MeSH
• glukosa-6-fosfátisomerasa MeSH
• proteiny huseníčku MeSH
• škrob MeSH