scholarly journals Variations in the activity of several enzymes in the mammary glands of non-pregnant, pregnant and lactating rabbits

1970 ◽  
Vol 116 (4) ◽  
pp. 657-661 ◽  
Author(s):  
P. E. Hartmann ◽  
E. A. Jones
Keyword(s):  
Mammary Gland ◽  
Small Mammals ◽  
Enzyme Activities ◽  
Mammary Glands ◽  
Acetyl Coa Carboxylase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Phosphogluconate Dehydrogenase ◽  
Citrate Lyase ◽  
Lactation Cycle

1. The enzymes phosphofructokinase (EC 2.7.1.11), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), phosphoglucomutase (EC 2.7.5.1), ATP–citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and acetyl-CoA synthetase (EC 6.2.1.1) were assayed in rabbit mammary glands at various stages of the pregnancy–lactation cycle. 2. The activities of all enzymes were low during pregnancy and, with the exception of phosphofructokinase, in non-pregnant animals. Two- to ten-fold increases in enzyme activities occurred over the first 20 days of lactation. Although milk yield was considerably decreased, the enzyme activities remained elevated in late lactation (45 days after parturition). 3. These findings are discussed in relation to mammary-gland metabolism and compared with similar observations previously made on ruminants and other small mammals.

scholarly journals Factors involved in changes in hepatic lipogenesis during development of the rat

1970 ◽  
Vol 118 (1) ◽  
pp. 155-162 ◽  
Author(s):  
Elizabeth A. Lockwood ◽  
E. Bailey ◽  
C. B. Taylor
Keyword(s):  
Enzyme Activities ◽  
Malic Enzyme ◽  
Hormonal Control ◽  
Male Rats ◽  
Acetyl Coa Carboxylase ◽  
Hepatic Enzymes ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Glucose 6 Phosphate Dehydrogenase

1. Changes in the activities of acetyl-CoA carboxylase (EC 6.4.1.2), phosphofructokinase (EC 2.7.1.11), aldolase (EC 4.1.2.13), extramitochondrial aconitate hydratase (EC 4.2.1.3) and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) have been measured in the livers of developing rats from late foetal life to maturity. 2. The effect of altering the weaning time on some enzymes associated with lipogenesis has been studied. Weaning rats at 15 days of age instead of 21 days results in an immediate increase in the activity of `malic' enzyme (EC 1.1.1.40) whereas the activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and ATP citrate lyase (EC 4.1.3.8) did not increase until 4–5 days and acetyl-CoA carboxylase 2–3 days after early weaning. Weaning rats on to an artificial-milk diet led to complete repression of the rise in activity of hepatic enzymes associated with lipogenesis normally found on weaning, except for `malic' enzyme, which increased in activity after 20 days of age. 3. The effect of intraperitoneal injections of glucagon, cortisol, growth hormone and thyroxine on the same hepatic enzymes has been investigated. Only thyroxine had any effect on enzyme activities and caused a 20-fold increase in `malic' enzyme activity and a twofold increase in ATP citrate lyase activity. 4. The activities of hepatic glucose 6-phosphate dehydrogenase and `malic' enzyme are higher in adult female than in adult male rats and it has been shown that this sex difference in enzyme activities is due to both male and female sex hormones. 5. Hepatic malate, citrate, pyruvate, glucose 6-phosphate and phosphoenolpyruvate concentrations have been measured throughout development. 6. The results are discussed in relation to the dietary and hormonal control of hepatic enzyme activities during development.

Metabolite levels and enzyme activities in the bovine mammary gland in different stages of lactation: II. Some metabolite levels and enzyme activities of the citric acid cycle

1973 ◽  
Vol 40 (3) ◽  
pp. 361-370 ◽  
Author(s):  
Marianne Waldschmidt ◽  
S. Rilling
Keyword(s):  
Mammary Gland ◽  
Isocitrate Dehydrogenase ◽  
Enzyme Activities ◽  
Citric Acid Cycle ◽  
Citrate Synthase ◽  
Bovine Mammary Gland ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Lactating Cows ◽  
Citrate Lyase

SummarySamples of the mammary gland were obtained by the freeze-clamping technique from heifers, lactating and dry cows. Levels of acetyl CoA, citrate, isocitrate and α-oxoglutarate were determined in extracts of the samples and calculated per g fresh gland and per mg DNA. All mammary metabolite levels were significantly higher in lactating cows than in heifers or dry cows. The accumulation in the lactating gland increased in the sequence acetyl CoA–α-oxoglutarate–isocitrate–citrate. NADP/NADPH ratios in cytoplasm, as calculated from the equilibrium of isocitrate dehydrogenase, were lowest in lactating glands. The activities of some enzymes were also determined in the cytoplasm and calculated per g fresh gland, per mg protein and per mg DNA. Mammary citrate synthase activity did not vary significantly between different groups of cattle, whereas mammary isocitrate dehydrogenase activity was higher in lactating cows than in heifers or dry cows. No activity of ATP citrate lyase was detected.

scholarly journals Initiation of lipogenic enzyme activities in rat mammary glands

1981 ◽  
Vol 198 (1) ◽  
pp. 187-192 ◽  
Author(s):  
P Martyn ◽  
I A Hansen
Keyword(s):  
Fatty Acid ◽  
Post Partum ◽  
Fatty Acid Synthetase ◽  
Mammary Glands ◽  
Synthetase Activity ◽  
Acetyl Coa Carboxylase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Stimulate Activity ◽  
Citrate Lyase

The activities of acetyl-CoA carboxylase, ATP citrate-lyase and fatty acid synthetase remained low until parturition at 22 days of gestation and increased significantly within 1 day post partum. Administration of progesterone on days 20 and 21 and at parturition abolished the increases for at least 48 h after parturition. Removal of the pups of normal rats prevented the increases in activities of acetyl-CoA carboxylase and ATP citrate-lyase, but not of fatty acid synthetase, and administration of prolactin corticosterone or insulin did not stimulate activity. Tissue from suckled glands in which the ducts had been ligated at parturition showed no increase in the activities of acetyl-CoA carboxylase and ATP citrate-lyase within 24 h, whereas fatty acid synthetase activity was similar to that in the sham-operated contralateral glands. Foetoplacentectomy on day 18 increased the activity of fatty acid synthetase but not of acetyl-CoA carboxylase and ATP citrate-lyase; suckling of these dams by foster pups increased both acetyl-CoA carboxylase and ATP citrate-lyase.

scholarly journals 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

1982 ◽  
Vol 204 (1) ◽  
pp. 273-280 ◽  
Author(s):  
Elizabeth M. McNeillie ◽  
Victor A. Zammit
Keyword(s):  
Mammary Gland ◽  
Enzyme Activities ◽  
Enzyme Concentration ◽  
Acetyl Coa Carboxylase ◽  
Initial Activity ◽  
Acetyl Coa ◽  
Activity Ratios ◽  
Rat Mammary Gland ◽  
Rate Limiting

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-α-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.

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

scholarly journals Studies on insulin-stimulated phosphorylation of acetyl-CoA carboxylase, ATP citrate lyase and other proteins in rat epididymal adipose tissue. Evidence for activation of a cyclic AMP-independent protein kinase

1984 ◽  
Vol 218 (3) ◽  
pp. 733-743 ◽  
Author(s):  
R W Brownsey ◽  
N J Edgell ◽  
T J Hopkirk ◽  
R M Denton
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
High Speed ◽  
Kinase Activity ◽  
Epididymal Adipose Tissue ◽  
Protein Kinase Activity ◽  
Acetyl Coa Carboxylase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Protein kinase activity in high-speed supernatant fractions prepared from rat epididymal adipose tissue previously incubated in the absence or presence of insulin was investigated by following the incorporation of 32P from [gamma-32P]ATP into phosphoproteins separated by sodium dodecyl sulphate/polyacrylamide-gel electro-phoresis. Incorporation of 32P into several endogenous proteins in the supernatant fractions from insulin-treated tissue was significantly increased. These included acetyl-CoA carboxylase and ATP citrate lyase (which exhibit increased phosphorylation within fat-cells exposed to insulin), together with two unknown proteins of subunit Mr 78000 and 43000. The protein kinase activity increased by insulin was distinct from cyclic AMP-dependent protein kinase, was not dependent on Ca2+ and was not appreciably affected by dialysis or gel filtration. The rate of phosphorylation of added purified fat-cell acetyl-CoA carboxylase and ATP citrate lyase was also increased by 60-90% in high-speed-supernatant fractions prepared from insulin-treated tissue. No evidence for any persistent changes in phosphoprotein phosphatase activity was found. It is concluded that insulin action on acetyl-CoA carboxylase, ATP citrate lyase and other intracellular proteins exhibiting increased phosphorylation involves an increase in cyclic AMP-independent protein kinase activity in the cytoplasm. The possibility that the increase reflects translocation from the plasma membrane, perhaps after phosphorylation by the protein tyrosine kinase associated with insulin receptors, is discussed.

Molecular biology of acetyl-CoA metabolism

2000 ◽  
Vol 28 (6) ◽  
pp. 591-593 ◽  
Author(s):  
B. J. Nikolau ◽  
D. J. Oliver ◽  
P. S. Schnable ◽  
E. S. Wurtele
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Decarboxylase ◽  
Acetyl Coa Carboxylase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Acetaldehyde Dehydrogenase ◽  
Citrate Lyase ◽  
Biochemical Genetic ◽  
Dehydrogenase Complex

We have characterized the expression of potential acetyl-CoA-generating genes (acetyl-CoA synthetase, pyruvate decarboxylase, acetaldehyde dehydrogenase, plastidic pyruvate dehydrogenase complex and ATP-citrate lyase), and compared these with the expression of acetyl-CoA-metabolizing genes (heteromeric and homomeric acetyl-CoA carboxylase). These comparisons have led to the development of testable hypotheses as to how distinct pools of acetyl-CoA are generated and metabolized. These hypotheses are being tested by combined biochemical, genetic and molecular biological experiments, which is providing insights into how acetyl-CoA metabolism is regulated.

Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung

1993 ◽  
Vol 265 (2) ◽  
pp. L140-L147 ◽  
Author(s):  
Z. X. Xu ◽  
W. Stenzel ◽  
S. M. Sasic ◽  
D. A. Smart ◽  
S. A. Rooney
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Fetal Lung ◽  
Acetyl Coa Carboxylase ◽  
Rat Lung ◽  
Acid Biosynthesis ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

There are developmental and glucocorticoid-induced increases in the rate of fatty acid biosynthesis and in the activity of fatty acid synthase in late gestation fetal lung. We have now measured mRNA levels of fatty acid synthase and of two other enzymes of fatty acid biosynthesis, ATP citrate lyase and acetyl-CoA carboxylase, in developing fetal and postnatal rat lung and in fetal lung explants cultured with and without dexamethasone. There was a developmental increase in the mRNA for fatty acid synthase with the maximum level being reached on fetal day 21 (term is fetal day 22). This profile was similar to that reported for de novo fatty acid synthesis and fatty acid synthase activity. There was a similar but less pronounced developmental increase in the mRNA for ATP citrate lyase and a corresponding increase in its activity. There was no developmental change in the mRNA for acetyl-CoA carboxylase. Dexamethasone increased the level of fatty acid synthase mRNA approximately threefold but had no effect on those for ATP citrate lyase and acetyl-CoA carboxylase. The effect of dexamethasone on fatty acid synthase mRNA was rapid, biphasic, and partly inhibited by actinomycin D and cycloheximide. We conclude that glucocorticoids increase expression of the gene for fatty acid synthase in fetal lung. The effect of the hormone appears to be due to increased transcription and post-transcriptional events and is dependent on protein synthesis.

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