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1.
Prior to birth the fetus of the rat accumulates large quantities of hepatic glycogen, with these stores mobilized as glucose in the early postnatal period to sustain the newborn until the onset of suckling and gluconeogenesis. The liver acts to mobilize glycogen in the early neonatal period and gradually adjusts to the alternating supply of nutrients that results from the onset of a feeding cycle. Early postnatal glycogen mobilization is reflected in the decreased active form of glycogen synthase (GS), the rate-limiting enzyme of glycogenesis, and increased activation of glycogen phosphorylase (GP), the rate-limiting enzyme of glycogenolysis. Levels of smooth endoplasmic reticulum (SER)-associated synthase phosphatase and phosphorylase phosphatase activities are diminished from high prenatal levels, contributing to these changes in activation of GS and GP. With the onset of suckling at 1-4 h after birth the liver again accumulates small quantities of glycogen. The period of 6 to 12 h after birth is characterized by large scale glycogenolysis. Glycogen levels are again increased at 24 h after birth, reflecting hepatic adaptation to the onset of meal feeding. 相似文献
2.
Hepatic carbon flux after re-feeding in the glycogen-storage-disease (gsd/gsd) rat. 总被引:2,自引:2,他引:0
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In this study we utilized the phosphorylase b kinase-deficient (gsd/gsd) rat as a model of hepatic substrate utilization where there is a constraint on glycogenesis imposed by the maintenance of high glycogen concentrations. Glucose re-feeding of 48 h-starved gsd/gsd rats led to suppression of hepatic glucose output. In contrast with the situation in normal rats, activation of the pyruvate dehydrogenase complex and lipogenesis was observed. It is suggested that impeding glycogenic flux may divert substrate into lipogenesis, possibly via activation of the pyruvate dehydrogenase complex. 相似文献
3.
Age-related augmentation of phosphorylase b kinase in hepatic tissue from the glycogen-storage-disease (gsd/gsd) rat. 总被引:2,自引:2,他引:0
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D G Clark S D Neville M Brinkman P V Nelson R J Illman A Guthberlet W D Haynes 《The Biochemical journal》1986,238(3):811-816
The effects of food deprivation on body weight, liver weight, hepatic glycogen content, glycogenolytic enzymes and blood metabolites were compared in young and old phosphorylase b kinase-deficient (gsd/gsd) rats. Although the concentration of glycogen in liver from 9-week-old female gsd/gsd rats (730 mumol of glucose equivalents/g wet wt.) was increased by 7-8% during starvation, total hepatic glycogen was decreased by 12% after 24 h without food. In 12-month-old male gsd/gsd rats the concentration of liver glycogen (585 mumol of glucose equiv./g wet wt.) was decreased by 16% and total hepatic glycogen by nearly 40% after food deprivation for 24 h. Phosphorylase b kinase and phosphorylase a were present at approx. 10% of the control activities in 9-week-old gsd/gsd rats, but both enzyme activities were increased more than 3-fold in 12-month-old affected rodents. It is concluded that the age-related ability to mobilize hepatic glycogen appears to result from the augmentation of phosphorylase b kinase during maturation of the gsd/gsd rat. 相似文献
4.
1. The total activity of glycogen synthease increased 20-fold from day 17 of gestation to birth at day 22, with a further increase of 18% in the 24h after birth. Active synthase (I) rose 45-fold to a maximum at day 21, fell 40% before birth, and then increased by a similar amount 24h after birth. The fraction of synthase in the active form correlated very well with the deposition of glycogen in the liver. 2. Total phosphorylase had a similar developmental pattern of total synthease with an 18-fold increase from day 17 to day 22. The appearance of active phosphorylase showed a lag-period compared with total phosphorylase and did not increase significantly until day 20. The fraction of phosphorylase in the active form did not correlate at all with glycogen deposition or mobilization. 3. There was a close relationshp between the ratio of phosphorylase a/synthase I and the glycogen content of the liver. An increase or decrease in this ratio would result in glycogenolysis of glycogenesis respectively. 4. It is postulated that a cycle between the two enzymes under basal conditions could exist which permits a continuous turnover of glycogen. Such a system would explain why active phosphorylase is always seen, even under conditions of net glycogen synthesis. The differences in hormone sensitivity of synthase and phosphorylase would also be accounted for as only one enzyme would have to respond acutely to hormonal influences. 相似文献
5.
Effects in vivo of food deprivation and 3-mercaptopicolinate in the glycogen-storage-disease (gsd/gsd) rat.
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Intraperitoneal injection of 3-mercaptopicolinate into 24 h-food-deprived 27-week-old female control (GSD/GSD) rats lowered the concentration of circulating glucose by 66%, but glycerol and lactate concentrations were increased up to 3- and 4-fold respectively. In phosphorylase b kinase-deficient (gsd/gsd) rats the corresponding changes for blood glucose, lactate and glycerol were half those observed in the controls. Although the concentration of liver glycogen (approx. 12%, w/w) in the gsd/gsd rats was not altered during food deprivation, total hepatic glycogen was decreased by 17%. It is suggested that the gradual breakdown of the extensive hepatic glycogen stores during starvation assists in the maintenance of normoglycaemia in the gsd/gsd rat. 相似文献
6.
Glycogen metabolism in isolated perfused rat liver 总被引:4,自引:0,他引:4
A K Walli G Siebler E Zepf H Schimassek 《Hoppe-Seyler's Zeitschrift für physiologische Chemie》1974,355(3):353-362
7.
The action of anoxia and cyanide on glycogen breakdown in the liver of the gsd/gsd rat 总被引:2,自引:0,他引:2
J V Conaglen R S Malthus J C Redshaw-Loten J G Sneyd 《European journal of biochemistry》1984,145(2):323-327
Perfusion of normal rat livers under anoxic conditions or the addition of KCN to aerobic perfusions activated phosphorylase and stimulated glycogen breakdown and glucose output. Livers from rats with a deficiency of liver phosphorylase kinase (gsd/gsd) showed a much smaller activation of phosphorylase with anoxia or KCN and produced glucose at about half the rate of normal livers. The increase in phosphorylase a in gsd/gsd livers was insufficient to account for the increase in glucose output. The addition of KCN to normal hepatocytes, activated phosphorylase and stimulated glucose output almost as effectively as glucagon. Hepatocytes from gsd/gsd rats showed only a very small increase in phosphorylase a on the addition of KCN, and glucose output did not increase. We conclude that in the perfused liver, anoxia and KCN stimulate glycogen breakdown and glucose output, at least in part, by a mechanism that does not involve conversion of phosphorylase b to phosphorylase a. In isolated hepatocytes KCN stimulates glucose output only by increasing the content of phosphorylase a. 相似文献
8.
9.
P R Walker 《Journal of cellular physiology》1977,91(2):169-179
Parenchymal cells were isolated from adult rat liver with an enzyme perfusion technique. The single-cell suspension, representing 40-50% of the liver's hepatocytes was suspended in medium and maintained in primary culture for up to four days. The cells were found to carry out glycogen synthesis for the first eight hours in culture after which time the accumulated glycogen was gradually degraded. The ability of the liver cell cultures to accumulate glycogen was found to be dependent upon the metabolic state of the animal prior to cell isolation. Cells prepared during the feeding period from animals on the 8+16 feeding schedule had markedly different capacities for glycogen accumulation. Changes in glycogen metabolism were found to be due, in part, to changes in the fraction of cells involved in metabolism at any given time. High concentrations of glucose stimulated the cells to deposit glycogen but the response was reduced the longer the cells were in culture over a 3-day period. This loss of glycogen synthesizing capacity appears to be due to a decrease in glycogen synthetase activity. The activities of pyruvate kinase, hexokinase and aldolase also decrease during the culture period. 相似文献
10.
11.
It has been reported that glycogen levels in retina vary with retinal vascularization. However, the electrical activity of isolated retina depends on glucose supply, suggesting that it does not contain energetic reserves. We determined glycogen levels and pyruvate and lactate production under various conditions in isolated retina. Ex vivo retinas from light- and dark-adapted rats showed values of 44 +/- 0.3 and 19.5 +/- 0.4 nmol glucosyl residues/mg protein, respectively. The glycogen content of retinas from light-adapted animals was reduced by 50% when they were transferred to darkness. Glycogen levels were low in retinas incubated in glucose-free media and increased in the presence of glucose. The highest glycogen values were found in media containing 20 mm of glucose. A rapid increase in lactate production was observed in the presence of glucose. Surprisingly, glycogen levels were the lowest and lactate production was also very low in the presence of 30 mm glucose. Our results suggest that glycogen can be used as an immediate accessible energy reserve in retina. We speculate on the possibility that gluconeogenesis may play a protective role by removal of lactic acid. 相似文献
12.
Hormonal regulation of L-type pyruvate kinase in hepatocytes from phosphorylase kinase-deficient (gsd/gsd) rats.
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The hormonal regulation of L-type pyruvate kinase in hepatocytes from phosphorylase b kinase-deficient (gsd/gsd) rats was investigated. Adrenaline (10 microM) and glucagon (10 nM) each led to an inactivation and phosphorylation of pyruvate kinase. Dose-response curves for adrenaline-mediated inactivation of pyruvate kinase, phosphorylation of pyruvate kinase and the stimulation of gluconeogenesis from 1.8 mM-lactate were similar for hepatocytes from control and gsd/gsd rats. Time-course studies indicated that adrenaline-mediated inactivation and phosphorylation of pyruvate kinase proceeded more slowly in phosphorylase kinase-deficient hepatocytes than in control hepatocytes. The age-dependent change in the adrenergic control of pyruvate kinase was similar between control and phosphorylase kinase-deficient hepatocytes. Adrenaline, glucagon and noradrenaline activated the cyclic AMP-dependent protein kinase and inhibited pyruvate kinase in phosphorylase kinase-deficient hepatocytes. Vasopressin (0.2-2 nM), angiotensin (10nM) and A23187 (10 microM) had no effect on the activity ratio of the cyclic AMP-dependent protein kinase or pyruvate kinase in these cells. It is concluded that phosphorylase kinase plays no significant role in the hormonal control of pyruvate kinase and that phosphorylation and inactivation of this enzyme results predominantly from the action of the cyclic AMP-dependent protein kinase. 相似文献
13.
Hisataka Shikama Motoyuki Yajima Michio Ui 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,631(2):278-288
Hepatic glycogen metabolism was studied in rats during the period of transition from the fed to fasted states. Glycogenic activity was measured in vivo based on the incorporation of [14C]glucose into liver glycogen. Its changes were almost parallel to the changes in glucogen synthase activity. Progressive accumulation of liver glycogen that occurred in the fed state was associated with a proportional increase in glycogenic activity. Within 4 h after the cessation of food intake, glycogenic activity showd a precipitous fall from the peak to its nadir without significant changes in glycogen content. Meanwhile, the glucose concentration in the portal vein decreased. Upon further development of fasting, glycogenic activity displayed a progressive regain, reciprocally as glycogen contents gradually decreased. The precipitous fall of glycogenic activity during the transition from the fed to fasted states was associated with a transient increase in plasma glucagon, and was partly overcome by the injection of anti-glucagon serum. It is concluded that the fall of portal venous concentration of glucose and secretion of glucagon act as a signal to initiate liver glycogen metabolism characteristics of the fasted or postabsorptive state. 相似文献
14.
15.
Hormonal regulation of glycogen metabolism in neonatal rat liver 总被引:5,自引:3,他引:2
1. The development of active and inactive phosphorylase was determined in rat liver during the perinatal period. No inactive form could be found in tissues from animals less than 19 days gestation or older than the fifth postnatal day. 2. The regulation of phosphorylase in organ cultures of foetal rat liver was examined. None of the agents examined [glucagon, insulin or dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate)] changed the amount of phosphorylase activity. 3. Glycogen concentration in these explants were nevertheless decreased more than twofold by 4h of incubation with glucagon or dibutyryl cyclic AMP. Incubation with insulin for 4h increased the glycogen content twofold. 4. Glycogen synthetase activity was examined in these explants. I-form activity (without glucose 6-phosphate) was found to decrease by a factor of two after 4h of incubation with dibutyryl cyclic AMP, whereas I+D activity (with glucose 6-phosphate) remained nearly constant. Incubation for 4h with insulin increased I-form activity threefold, with only a slight increase in I+D activity. 5. When explants were incubated with insulin followed by addition of dibutyryl cyclic AMP, the effects of insulin on glycogen concentration and glycogen synthetase activity were reversed. 6. These results indicate that the regulation of glycogen synthesis may be the major factor in the hormonal control of glycogen metabolism in neonatal rat liver. 相似文献
16.
17.
Activation of hepatic glycogen phosphorylase b in vivo by sodium sulphate in normal (Wistar) and phosphorylase b kinase-deficient (gsd/gsd) rats.
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Sulphate ions have been known for some years to enhance the activity of hepatic glycogen phosphorylase b in vitro. Here we report that intravenous injections of 4.92 mmol of Na2SO4/kg body wt. to rats induced marked hepatic glycogenolysis in vivo, accompanied by polyuria, glycosuria and a mild hyperglycaemia. These effects were observed both in normal (Wistar) rats and in gsd/gsd rats that lacked hepatic phosphorylase kinase. In both rat strains the activity of glycogen phosphorylase in liver extracts was enhanced by pretreatment of the animals with Na2SO4, but in phosphorylase kinase-deficient livers the enhancement was solely in phosphorylase b activity, whereas both the a and b forms of the enzyme were activated in normal livers. Hepatic glycogenolysis was also induced by perfusing rat livers, both normal and gsd/gsd, with 25 mM-Na2SO4. Under these conditions both the rat strains showed only enhanced activities of glycogen phosphorylase b. This suggested that the increased activity of phosphorylase a in the extracts of normal livers after Na2SO4 administration in vivo was due to a hormonally mediated conversion of the b form into the a form. The activation of glycogen phosphorylase b was stable to dilution and appeared to be due to a long-lasting structural change in the enzyme or very tight binding of an activator. 相似文献
18.
R N Margolis 《Biochemical and biophysical research communications》1985,126(3):1215-1221
Glycogen synthase first appears in significant levels in fetal rat liver on day 18 of gestation (22 day term), but in a mostly inactive, phospho- form. This was reflected in a decreased affinity for its allosteric activator (increased A0.5 for glucose-6-phosphate), and with limited glycogen synthesis and accumulation. Peak glycogen synthesis occurs on day 21 of gestation, and glycogen synthase is in a more dephospho-form with decreased A0.5 for G6P and increased -G6P/+G6P activity ratio. The data suggest that a significant change in phosphorylation state of synthase occurs in late gestation to facilitate the large increase in glycogen synthesis and accumulation. 相似文献
19.
20.
J T Brosnan M E Brosnan M Yudkoff I Nissim Y Daikhin A Lazarow O Horyn I Nissim 《The Journal of biological chemistry》2001,276(34):31876-31882
We have utilized [(15)N]alanine or (15)NH(3) as metabolic tracers in order to identify sources of nitrogen for hepatic ureagenesis in a liver perfusion system. Studies were done in the presence and absence of physiologic concentrations of portal venous ammonia in order to test the hypothesis that, when the NH(4)(+):aspartate ratio is >1, increased hepatic proteolysis provides cytoplasmic aspartate in order to support ureagenesis. When 1 mm [(15)N]alanine was the sole nitrogen source, the amino group was incorporated into both nitrogens of urea and both nitrogens of glutamine. However, when studies were done with 1 mm alanine and 0.3 mm NH(4)Cl, alanine failed to provide aspartate at a rate that would have detoxified all administered ammonia. Under these circumstances, the presence of ammonia at a physiologic concentration stimulated hepatic proteolysis. In perfusions with alanine alone, approximately 400 nmol of nitrogen/min/g liver was needed to satisfy the balance between nitrogen intake and nitrogen output. When the model included alanine and NH(4)Cl, 1000 nmol of nitrogen/min/g liver were formed from an intra-hepatic source, presumably proteolysis. In this manner, the internal pool provided the cytoplasmic aspartate that allowed the liver to dispose of mitochondrial carbamyl phosphate that was rapidly produced from external ammonia. This information may be relevant to those clinical situations (renal failure, cirrhosis, starvation, low protein diet, and malignancy) when portal venous NH(4)(+) greatly exceeds the concentration of aspartate. Under these circumstances, the liver must summon internal pools of protein in order to accommodate the ammonia burden. 相似文献