Control of Glycogen Content in Retina: Allosteric Regulation of Glycogen Synthase

Retinal tissue is exceptional because it shows a high level of energy metabolism. Glycogen content represents the only energy reserve in retina, but its levels are limited. Therefore, elucidation of the mechanisms controlling glycogen content in retina will allow us to understand retina response under local energy demands that can occur under normal and pathological conditions. Thus, we studied retina glycogen levels under different experimental conditions and correlated them with glucose-6-phosphate (G-6-P) content and glycogen synthase (GS) activity

Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm−/−). Here, we show that Pfkm−/− mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm−/− mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm−/− mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm−/− mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies

The Metallicity Distribution of Late-Type Dwarfs and the Hipparcos HR Diagram

The Hipparcos Catalogue provides an accurate and extensive sampling of the solar neighbourhood HR diagram. The morphology of this diagram depends on selection criteria of the catalogue such as the limiting magnitude, and on the characteristics of the stellar populations near the Sun (space density, metallicity, star formation rate, etc). We present our first results on the local stellar populations, obtained from the study of a well defined, accurate (but restricted) sample. Using a sample of G and K dwarfs, we define the local metallicity distribution of long-lived stars in the solar neighbourhood, and discuss the resulting metallicity distribution and the kinematic properties of the sample. These results will be used in a model of the local galactic stellar populations. This model is briefly presented, and will be used to analyse the accurate multidimensional data now available for the Hipparcos survey stars. Key words: Hipparcos HR diagram; dwarfs metallicity distribution; Star Form..