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Since the discovery of Na/K-ATPase by Skou, the mechanism of Na/K-dependent ATP hydrolysis and Na and K transport has been extensively studied. The hydrolysis appears to occur sequentially via the Na-Enzyme-ATP complex (NaE1ATP), ADP-sensitive phosphoenzyme (NaE1P), the K-sensitive phosphoenzyme (E2P) and the K-occluded enzyme (KE2), known the Post-Albers mechanism, in a protomer or diprotomer that consists of alpha- and beta-chains. The tetrameric nature of the enzyme such as a quarter, half, third to fourth and full site reactivity and the visualization by electron microscopy show direct biochemical evidence for the presence of a tetraprotomer structure of Na/K-ATPase during ATP hydrolysis. ATP binding is followed by two parallel paths, which occur at each of the two half sites for phosphorylation-dephosphorylation, and direct ATP hydrolysis via (NaE1P : E.ATP)2, (E2P : E.ATP : E2P : E.ADP/Pi) and (KE2 : E.ADP/Pi)2, respectively. The sequential formation of E2P from NaE1P and KE2 from E2P is accompanied by, respectively, hydrolysis of half of the TCA-labile bound ATP to ADP/Pi and of another half of the bound ATP to ADP/Pi. All reaction intermediates detectable in the Post-Albers scheme bind ATP and/or ADP/Pi.

We reported two cases of brothers demonstrating oculopharyngeal muscular dystrophy (OPMD). The cases had consanguineous parents and five healthy siblings, which suggested the autosomal recessive inheritance. The initial symptom was slowly progressive blepharoptosis with onset in the third decade. On examination, total external ophthalmoplegia was observed in both patients. Additionally, the elder, a 57-year-old man, exhibited dysarthria, dysphagia and muscular weakness with atrophy of the face, bilateral proximal upper limbs and diffuse lower limbs. The younger brother, a 55-year-old man, displayed muscular weakness and atrophy distributed in the face and four limbs. Muscle biopsy of both cases revealed rimmed vacuoles and spheroid bodies in the atrophic and normal-sized fibers. Biochemical study of the biopsy specimens of the elder brother disclosed the myophosphorylase activity reduced to about 40% of the normal value, although in the younger brother, that activity was normal. OPMD is usually inherited in the autosomal dominant mode, and autosomal recessive OPMD is rare. The onset age of our cases was younger than that of the autosomal dominant OPMD. There were some differences in the clinical manifestation between the presented cases, which could be interpreted as phenotypic variation. The elder brother was thought to be associated with McArdle's disease.

To elucidate the effect of the antiprogesterone steroid RU 486 (RU) on endometrial glycogen metabolism, a dose of 30 mg/kg of the agent was administered to pregnant rats on Day 2 (group 1) or Day 4 (group 2) of pregnancy, and glycogen content, glycogen synthetase (GS) and glycogen phosphorylase (GP) activities in the endometrium were investigated on Day 6. In addition, serum ovarian steroid hormones and the number of implantation sites were evaluated. The glycogen content in the endometrium in group 1 and group 2 decreased significantly (p less than 0.02 and p less than 0.05) compared with the control group. The total GS activity in the endometrium in group 1 decreased significantly (p less than 0.05). On the other hand, the independent GS activity in group 2 increased significantly (p less than 0.05) compared with the control group. The active GP activity in group 1 increased markedly, and the total GP activity increased significantly (p less than 0.05) compared with the control value. In group 2, the active and total GP activities increased significantly (p less than 0.01 and p less than 0.02) compared with the control values. Serum progesterone (P) concentrations in group 1 and group 2 were significantly (p less than 0.05 and p less than 0.05) lower than those in the control groups 2 days after the RU administration, and implantations were significantly (p less than 0.01 and p less than 0.01) inhibited. These results suggest that RU 486 affects endometrial glycogen metabolism, resulting in the prevention of implantation.

Characteristic of insulin receptor in human placental villi with relation to glucose uptake and glycogenesis was studied in vitro. The specific binding of 125I-insulin to placental villi membranes was measured significantly higher in early placenta than in term placenta, while Scatchard plots analysis showed curvilinear, which indicated the binding affinity was approximately the same between them. However the binding capacity was higher in early placenta than in term placenta. The addition of insulin to placental villi in vitro showed increased glucose uptake, glycogen content and glycogen synthetase I form activity both in early and term placental villi. The glucose uptake, glycogen content and glycogen synthetase (total and I form) activity were higher in early placental villi than in term placental villi, but there was no significant difference in glycogen phosphorylase (total and active form). Collectively, the data suggest the presence of insulin receptor in placental villi varying its concentration with gestational age, where insulin plays a role in adjusting glucose uptake and glycogenesis.

Rat fetal brain glycogen content, and glycogen synthase and phosphorylase activities were measured both in control and in hypoxia on 17th, 19th and 21st days of gestation. Glycogen distribution in the brain was also observed with an optical microscope. The results obtained were as follows: 1. Glycogen content was highest in the choroid plexus, and there tended to be located more in the periventricular areas and hemispheric surface layers of the cerebrum than in other areas. 2. Glycogen content increased from the 17th day, reaching a peak on the 19th day; it decreased with age thereafter and had decreased significantly by the 21st day. 3. Glycogen synthase a-type activity showed no change with fetal age. 4. Glycogen phosphorylase activity was lowest on the 17th day, and it increased thereafter with age. 5. When an ischemic load was applied, brain glycogen content decreased and glycogen phosphorylase a-type activity increased on the 17th and 19th days. The abovementioned findings suggest that glycogen in the rat fetal brain is distributed in the most likely sites of intracranial hemorrhage. The amount of glycogen in the rat fetal brain may depend on glycogen phosphorylase activities. Glycogen may be used as an energy source to maintain brain tissue function during hypoxia. It is also possible that glycogen plays a role in brain maturation.

Fetal liver glycogen content, glycogen synthetase and phosphorylase activity were measured in growth retarded fetuses on 20th day of gestation of pregnant rats. The effects of administration of dexamethasone to the mother were also examined in both enzyme activities in livers of fetal rats. The results obtained were as follows. The incidence of IUGR rats by ligation of maternal uterine vessels on the 17th day of gestation was 85.8%. No changes in fetal body and liver weights were found after the administration of dexamethasone to the mother. In the IUGR fetuses, liver glycogen content was decreased about 25% compared with the control. However, the decreased liver glycogen levels in IUGR fetuses increased to the control level following the administration of dexamethasone. In IUGR fetuses, liver glycogen synthetase activity of both a-form and a + b form decreased. Dexamethasone markedly increased the a-form of glycogen synthetase. The effects of dexamethasone in glycogen phosphorylase activity of fetal liver were unchanged in IUGR fetuses.

Effects of coronary artery ligation on myocardial glycogenolysis were studied in the endo- and epicardial layers of the left ventricular wall in dogs pretreated with 10 or 100 microgram/kg (i.v.) of carteolol, a potent beta-adrenergic blocking agent. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. In control (saline-pretreated) dogs, an increase in phosphorylase alpha activity and an increase in breakdown of glycogen were observed in both endo- and epicardial layers after coronary artery ligation. In the presence of 10 or 100 microgram/kg of carteolol, however, increases in phosphorylase alpha activity and increase in breakdown of glycogen were not observed in either the endo or epicardial layers. These results indicate that pretreatment of the dog with carteolol inhibits the increase in glycogenolysis caused by coronary artery ligation. Nevertheless, carteolol did not completely inhibit the coronary artery ligation-induced increase in glucose-6-phosphate and lactate levels, and the coronary artery ligation-induced decrease in phosphocreatine level, particularly in the endocardial layers.

Glycogen content, glycogen synthetase and glycogen phosphorylase were studied in the endometrial tissues of 28 women with normal menstrual cycles and in the decidual tissues of 24 women with normal early pregnancies. The endometrial glycogen synthetase enzyme increased gradually from the proliferative phase to the secretory phase and reached maximal activity during the sixteenth to twenty-third days of the cycle, a time coincident with maximal glycogen content, while the glycogen phosphorylase reached its maximal activity on and after the twenty-fourth day of the cycle. In addition, glycogen phosphorylase activity in the decidual tissue during the early period of gestation (4--10 weeks) was lower than that in the endometrial tissue during the late secretory phase of the cycle, and in particular, the active form (-AMP) was significantly (p less than 0.005) low, with the result that the glycogen content in the decidua was significantly (p less than 0.05) higher than that in the endometrium. On the other hand, in 20 normal pregnant women during the 6--10th weeks of gestation, the glycogen contents in the decidua and in the placental villi were 599 +/- 44 mg/100 g wet weight (mean +/- standard error of the mean) and 731 +/- 55 mg/100 g, respectively, but the difference between them was statistically not significant. The levels of glycogen synthetase and glycogen phosphorylase enzyme in the decidua were significantly (p less than 0.005) higher than those in the placental villi.