Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid inhibition of acetyl-CoA carboxylase (ACC) activity in rat liver in response to 6 h starvation and rapid re-activation in response to 2-6 h of re-feeding chow were shown to be due to changes in the expressed activity of existing enzyme. Decreases and increases in ACC concentration occurred at later stages of the transitions, i.e. 6-48 h starvation and 8-24 h re-feeding respectively. The decrease in expressed activity of ACC was due primarily to changes in its phosphorylation state, demonstrated by a significantly decreased Vmax. and significantly increased Ka for citrate of enzyme purified by avidin-Sepharose chromatography from 6 h- or 48 h-starved rats. These effects were totally reversed within 2-4 h of chow re-feeding. Changes in the activity of purified ACC closely correlated with reciprocal changes in the activity of AMP-activated protein kinase (AMP-PK) over the fed to starved to re-fed transition. Increases in the activity ratio of cyclic-AMP-dependent protein kinase in response to starvation lagged behind the increase in AMP-PK and the decrease in ACC activity. Changes in AMP-PK and ACC activities of rat liver closely correlated with changes in plasma insulin concentration in response to time courses of starvation and re-feeding.
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PMID:The short-term regulation of hepatic acetyl-CoA carboxylase during starvation and re-feeding in the rat. 168 93

1. Withdrawal of food from lactating rats produced a rapid and dramatic decrease in the uptake of glucose by the mammary gland and an inhibition of the rate of fatty acid synthesis that could not be explained alone by decreased substrate supply to the tissue. 2. Within the first 6 hr starvation, fatty acid synthesis and pyruvate dehydrogenase activity were inhibited by 87 and 80%, respectively, but acetyl-CoA carboxylase activity did not change significantly. 3. Between 6 and 24 hr starvation, total and expressed activities of acetyl-CoA carboxylase decreased by 62 and 55%, respectively. 4. The ratio of fructose-6-phosphate/fructose-1,6-bisphosphate concentration in mammary tissue increased 9-fold during the first 6 hr starvation, indicating an inhibition of 6-phosphofructo-1-kinase. However, the major inhibition of this enzyme occurred between 6 and 24 hr starvation when this metabolite ratio increased a further 160-fold in parallel with increased tissue citrate concentration. 5. The increase in citrate concentration between 6 and 24 hr starvation correlated with acetyl-CoA carboxylase inactivation and ketone body accumulation in the mammary gland. 6. This study confirms the asynchronous control of three important regulatory steps in the pathway of glucose utilization and fatty acid synthesis in the lactating rat mammary gland.
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PMID:Regulation of fatty acid synthesis in lactating rat mammary gland in the fed to starved transition: asynchronous control of pyruvate dehydrogenase, phosphofructokinase and acetyl-CoA carboxylase. 168 75

The role of cyclic AMP in acute regulation of the metabolism of mammary tissue in the lactating rat was examined by measuring the activity ratio of cyclic AMP-dependent protein kinase (A-kinase) and by examining the properties of this enzyme in its two major isoenzymic forms. Isoenzyme II is the major form in soluble extracts of rat mammary tissue. A-kinase activity ratio in such extracts is unaffected by starvation of the lactating rat. Treatment of the intact rat with isoprenaline, or addition of isoprenaline to incubations in vitro of mammary acini, resulted in a major increase in the activity ratio of A-kinase. These treatments equally affected isoenzymes I and II. The treatment in vitro lead to a rapid depletion of A-kinase as subsequently measured in extracts of acini. The degree of activation of the enzymes acetyl-CoA carboxylase and glycogen phosphorylase in extracts of mammary tissue and of acini was assessed as a function of these treatments. The increased activation of A-kinase induced by isoprenaline was unaccompanied by significant changes in the activity of acetyl-CoA carboxylase in acini, although we previously showed that this agent activates acetyl-CoA carboxylase in intact mammary tissue. Contrastingly, isoprenaline-induced enhancement of A-kinase activity was accompanied by an increase in the activity ratio of phosphorylase in acini. These results indicate that: (a) a normal response of expressed A-kinase activity to cyclic AMP operates in mammary acini and mammary tissue from lactating rats; (b) rapid modulation of the total amount of soluble A-kinase is mediated in mammary epithelial cells by cyclic AMP; (c) phosphorylase, an ultimate target of the protein phosphorylation cascade initiated by A-kinase, is activated in acini under conditions where A-kinase activity is enhanced; and (d) mechanisms other than that of the A-kinase phosphorylation/inhibition model for acetyl-CoA carboxylase regulation must operate in mammary tissue preparations and in vivo to account for the response of this enzyme to enhanced A-kinase activity.
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PMID:Cyclic AMP-dependent protein kinase in mammary tissue of the lactating rat. Activity ratio and responsiveness of the target enzymes acetyl-CoA carboxylase and glycogen phosphorylase to beta-adrenergic stimulation. 196 34

Food intake, plasma glucose, insulin (I) and triiodothyronine (T3) and liver glucose 6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME). ATP-citrate lyase, acetyl-CoA carboxylase (AcCoACx) and fatty acid synthase (FAS) activities were measured in 2 and 22 months old rats before, after 3 d starvation and 2,4,6. 24 and 48 h refeeding a high carbohydrate (74% w/w) diet. Expressed per 100 g of body weight, the carbohydrate intake of old rats was 55% lower than that of young rats. Plasma insulin was higher in old than in young rats and decreased (-40%) after starvation and returned to control values 4 h after refeeding. In young rats plasma insulin fell after starvation (-85%) and returned to normal values 2 h after refeeding. No significant differences were observed in plasma [T3] between the two groups. During the first 6 h of refeeding, plasma glucose increased 2-fold and returned to control values after 24 h in young rats. In old rats, plasma glucose returned to its control value after 2 h. Compared to the starved level, 48 h after refeeding, G6P-DH, ME, ATP-citrate lyase, AcCoACx and FAS activities increased 5- to 6-fold in young rats, while in old rats the increase was much smaller and represented 35% of that observed in young rats. These results suggest, that the age-related reduction in inducibility of hepatic lipogenic enzymes of rats refed a high carbohydrate diet after starvation may be due to a spontaneous decrease in the carbohydrate intake and to a decrease effectiveness of insulin (insulin resistance).
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PMID:Age-dependent hepatic lipogenic enzyme activities in starved-refed rats. 197 51

We have used the cold-clamping technique to study the changes in acetyl-CoA carboxylase activity that occur in the cytosolic and mitochondrial fractions of the liver of fed, starved and starved-refed rats. No evidence was found for a role of the mitochondrial enzyme as a pool from which cytosolic carboxylase could be replenished upon refeeding of starved rats. Starvation for 24 h or 48 h induced changes in the expressed (assayed at 20 mM-citrate), total (citrate- and phosphatase-treated) and citrate-independent activities of cytosolic carboxylase, as well as in its Ka for citrate. The expressed/total activity ratio was low even in the fed state and was depressed further by starvation. The effects of refeeding occurred in two phases: an acute phase (approx. 1 h) in which the starvation-induced changes in Ka and expressed/total activity ratio were rapidly reversed, and a prolonged slow phase in which the two parameters attained values that were lower and higher, respectively, than those in the normal fed state. Refeeding also resulted in a gradual increase in citrate-independent activity of acetyl-CoA carboxylase. An additional marked increase in this activity occurred only in 48 h-starved-refed rats between 24 h and 48 h of refeeding. These findings are discussed in terms of the observed time courses of changes in lipogenic rates that occur in vivo in starved-refed rats and of the possible molecular mechanisms involved.
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PMID:Changes in the properties of cytosolic acetyl-CoA carboxylase studied in cold-clamped liver samples from fed, starved and starved-refed rats. 198 63

The relative amounts of mRNAs coding for fatty-acid synthase (EC 2.3.1.85), acetyl-CoA carboxylase (EC 6.4.1.2), ATP citrate lyase (EC 4.1.3.8) and malic enzyme (EC 1.1.1.40) were determined in lungs and livers of adult rats that were normally fed, starved for 48 h or starved for 48 h and subsequently refed for 72 h with a carbohydrate-rich, fat-free diet. In the liver, starvation caused a small decrease in the relative abundance of the mRNAs which was not statistically significant. Subsequent refeeding caused a statistically significant increase in mRNAs for all of the enzymes studied. In the lung, no significant changes were found, indicating that the regulation of the abundance of mRNAs encoding the lipogenic enzymes in the lung differs from that in the liver. In the developing rat lung, mRNA for fatty-acid synthase increased 3-fold in abundance between fetal days 18 and 20 and decreased directly after birth (at day 22 of gestation). A similar pattern was observed for ATP citrate lyase mRNA. The level of acetyl-CoA carboxylase mRNA decreased significantly after birth. These observations indicate that in perinatal rat lungs, pretranslational regulation is involved in the control of the synthesis of these enzymes. The abundance of acetyl-CoA carboxylase mRNA did not change in the prenatal period, a time during which the specific activity of this enzyme increases. This lack of correlation between the specific activity of acetyl-CoA carboxylase and the abundance of its mRNA may indicate that translational regulation of the synthesis of the enzyme or post-synthetic regulatory effects on enzyme molecules are involved in the control of this enzyme in the prenatal period. No changes in the abundance of lung malic enzyme mRNAs were observed throughout the perinatal period.
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PMID:Levels of mRNAs coding for lipogenic enzymes in rat lung upon fasting and refeeding and during perinatal development. 257 95

Activation of acetyl-CoA carboxylase during incubation of crude extracts of lactating rat mammary gland with Mg2+ and citrate can be blocked by NaF, suggesting that it represents a dephosphorylation of the enzyme. The greater extent of activation in extracts from 24 h-starved rats (200%) compared with fed controls (70%) implies that the decrease in acetyl-CoA carboxylase activity in response to 24 h starvation may involve increased phosphorylation of the enzyme. Acetyl-CoA carboxylase was purified from the mammary glands of lactating rats in the presence of protein phosphatase inhibitors by avidin-Sepharose chromatography. Starvation of the rats for 24 h increased the concentration of citrate giving half-maximal activation by 75%, and decreased the Vmax. of the purified enzyme by 73%. This was associated with an increase in the alkali-labile phosphate content from 3.3 +/- 0.2 to 4.5 +/- 0.4 mol/mol of enzyme subunit. Starvation of lactating rats for 6 h, or short-term insulin deficiency induced by streptozotocin injection, did not effect the kinetic parameters or the phosphate content of acetyl-CoA carboxylase purified from mammary glands. The effects of 24 h starvation on the kinetic parameters and phosphate content of the purified enzyme were completely reversed by re-feeding for only 2.5 h. This effect was blocked if the animals were injected with streptozotocin before re-feeding, suggesting that the increase in plasma insulin that occurs on re-feeding was responsible for the activation of the enzyme. The effects of re-feeding 24 h-starved rats on the kinetic parameters and phosphate content of acetyl-CoA carboxylase could be mimicked by treating enzyme purified from 24 h-starved rats with protein phosphatase-2A in vitro. Our results suggest that, in mammary glands of 24 h-starved lactating rats, insulin brings about a dephosphorylation of acetyl-CoA carboxylase in vivo, which may be at least partly responsible for the reactivation of mammary lipogenesis in response to re-feeding.
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PMID:The role of acetyl-CoA carboxylase phosphorylation in the control of mammary gland fatty acid synthesis during the starvation and re-feeding of lactating rats. 287 30

1. The effect of nutritional status on fatty acid synthesis in brown adipose tissue was compared with the effect of cold-exposure. Fatty acid synthesis was measured in vivo by 3H2O incorporation into tissue lipids. The activities of acetyl-CoA carboxylase and fatty acid synthetase and the tissue concentrations of malonyl-CoA and citrate were assayed. 2. In brown adipose tissue of control mice, the tissue content of malonyl-CoA was 13 nmol/g wet wt., higher than values reported in other tissues. From the total tissue water content, the minimum possible concentration was estimated to be 30 microM 3. There were parallel changes in fatty acid synthesis, malonyl-CoA content and acetyl-CoA carboxylase activity in response to starvation and re-feeding. 4. There was no correlation between measured rates of fatty acid synthesis and malonyl-CoA content and acetyl-CoA carboxylase activity in acute cold-exposure. The results suggest there is simultaneous fatty acid synthesis and oxidation in brown adipose tissue of cold-exposed mice. This is probably effected not by decreases in the malonyl-CoA content, but by increases in the concentration of free long-chain fatty acyl-CoA or enhanced peroxisomal oxidation, allowing shorter-chain fatty acids to enter the mitochondria independent of carnitine acyltransferase (overt form) activity.
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PMID:Regulation of fatty acid synthesis and malonyl-CoA content in mouse brown adipose tissue in response to cold-exposure, starvation or re-feeding. 288 57

The effects of Triton WR 1339, starvation and cholesterol diet on the activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and acetyl-CoA carboxylase and on the rates of mevalonic acid (MVA) biosynthesis from acetyl-CoA and malonyl-CoA in the soluble (140 000 g) and microsomal fractions of rat liver, on the rate of incorporation of these substrates into squalene, cholesterol and lanosterol in the rat liver postmitochondrial fraction and on the rate of fatty acid biosynthesis was studied. The administration of Triton WR 1339 (200 mg per 100 g of body weight twice) stimulated the activity of HMG-CoA reductase and MVA biosynthesis from acetyl-CoA and malonyl-CoA in the intact and solubilized microsomal fractions and had no effect on these parameters in the soluble fraction. Starvation for 36 hrs did not cause inhibition of the reductase activity or MVA biosynthesis from both substrates in the soluble fraction. Alimentary cholesterol significantly increased the activity of HMG-CoA reductase, had no effect on the rate of MVA biosynthesis from acetyl-CoA and stimulated the malonyl-CoA incorporation in to MVA in the soluble fraction. Starvation an alimentary cholesterol inhibited the HMG-CoA reductase activity and MVA biosynthesis from both substrates in the solubilized microsomal fraction. Triton WR 1339 stimulated 4--19-fold the lipid formation in the total unsaponified fraction and its components i.e. squalene, lanosterol, cholesterol, from acetyl-CoA and only insignificantly (1,2--1,7-fold) increased malonyl-CoA incorporation into these compounds. Starvation and alimentary cholesterol repressed lanosterol and cholesterol biosynthesis from acetyl-CoA, decreased malonyl-CoA incorporation into these sterols and had no influence on squalene biosynthesis from the two substrates. Triton WR 1339 and starvation inhibited the acetyl-CoA carboxylase activity, unaffected by alimentary cholesterol. No significant changes in the rate of fatty acid biosynthesis from the substrates were observed. The data obtained provide evidence for the existence of autonomic pathways of MVA biosynthesis localized in the soluble and microsomal fractions of rat liver. The pathway of MVA biosynthesis in the soluble fraction is less sensitive to regulatory factors. Sterol biosynthesis from malonyl-CoA is also more resistant to regulatory effects than sterol biosynthesis from acetyl-CoA. This suggests that HMG-CoA reductase localized in the soluble fraction takes part in MVA and sterol biosynthesis from malonyl-CoA.
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PMID:[Activities of 3-hydroxyl-3-methylglutaryl-CoA reductase and acetyl-CoA carboxylase and the rate of mevalonic acid, squalene, sterol and fatty acid biosynthesis from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in rat liver: effects of Triton WR 1339, starvation and cholesterol diet]. 611 54

The ;initial' (I), endogenous phosphatase-activated (A) and citrate-activated (C) activities of acetyl-CoA carboxylase were measured in mammary-gland extracts of pregnant and lactating rats. There was a 10-fold increase in the A and C enzyme activities in the transition from early to peak lactation [cf. data of Mackall & Lane (1977) Biochem. J.162, 635-642], but there was no significant increase in the ratio of the initial activity to the A and C activities of the enzyme. Starvation (24h) or short-term (3h) streptozotocin-induced diabetes both resulted in a 40% decrease in I/A and I/C activity ratios. In starvation this was accompanied by a decrease in the absolute values of the A and C activities such that the initial activity in mammary glands of starved animals was 45% that in glands from fed animals. Insulin treatment of starved or diabetic animals 60min before killing increased the I activity without affecting the A or C enzyme activities. Removal of the pups for 24h from animals in peak lactation (weaning) resulted in a marked but similar decrease in all three activities such that, although the initial activity was only 10% of that in suckled animals, the I/A and I/C activity ratios remained high and unaltered. Inhibition of prolactin secretion by injection of 2-bromo-alpha-ergocryptine gave qualitatively similar results to those during weaning. Simultaneous administration of ovine prolactin completely prevented the effects of bromoergocryptine. It is suggested that the initial activity of acetyl-CoA carboxylase in rat mammary gland is regulated by at least two parallel mechanisms: (i) an acute regulation of the proportion of the enzyme in the active state and (ii) a longer-term modulation of enzyme concentration in the gland. Insulin appeared to mediate its acute effects through mechanism (i), whereas prolactin had longer-term effects on enzyme concentration in the gland. A comparison of initial enzyme activities (I) obtained in the present study with rates of lipogenesis measured in vivo [Agius & Williamson (1980) Biochem. J.192, 361-364; Munday & Williamson (1981) Biochem. J.196, 831-837] gave good agreement between the two sets of data for all conditions studied except for 24h-starved and streptozotocin-diabetic animals. It is suggested that acetyl-CoA carboxylase activity is rate-limiting for lipogenesis in the mammary gland in normal, fed, suckled or weaned animals but that in starved and short-term diabetic animals changes in the activity of the enzyme by covalent modification alone may not be sufficient to maintain the enzyme in its rate-limiting role.
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PMID:Regulation of acetyl-CoA carboxylase in rat mammary gland. Effects of starvation and of insulin and prolactin deficiency on the fraction of the enzyme in the active form in vivo. 612 84


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