scholarly journals Metabolic Fate of the Increased Yeast Amino Acid Uptake Subsequent to Catabolite Derepression

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
John S. Hothersall ◽  
Aamir Ahmed
Keyword(s):  
Amino Acid ◽  
Protein Expression ◽  
Citrate Synthase ◽  
Tca Cycle ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Leucine Oxidation ◽  
The Tca Cycle ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Catabolite repression (CCR) regulates amino acid permeases in Saccharomyces cerevisiae via a TOR-kinase mediated mechanism. When glucose, the preferred fuel in S. cerevisiae, is substituted by galactose, amino acid uptake is increased. Here we have assessed the contribution and metabolic significance of this surfeit of amino acid in yeast undergoing catabolite derepression (CDR). L-[U-14C]leucine oxidation was increased 15 ± 1 fold in wild type (WT) strain grown in galactose compared to glucose. Under CDR, leucine oxidation was (i) proportional to uptake, as demonstrated by decreased uptake and oxidation of leucine in strains deleted of major leucine permeases and (ii) entirely dependent upon the TCA cycle, as cytochrome c1 (Cyt1) deleted strains could not grow in galactose. A regulator of amino acid carbon entry into the TCA cycle, branched chain ketoacid dehydrogenase, was also increased 29 ± 3 fold under CCR in WT strain. Protein expression of key TCA cycle enzymes, citrate synthase (Cs), and Cyt1 was increased during CDR. In summary, CDR upregulation of amino acid uptake is accompanied by increased utilization of amino acids for yeast growth. The mechanism for this is likely to be an increase in protein expression of key regulators of the TCA cycle.

scholarly journals Prolonged amino acid infusion into intrauterine growth-restricted fetal sheep increases leucine oxidation rates

2018 ◽  
Vol 315 (6) ◽  
pp. E1143-E1153 ◽  
Author(s):  
Sandra G. Wai ◽  
Paul J. Rozance ◽  
Stephanie R. Wesolowski ◽  
William W. Hay ◽  
Laura D. Brown
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Intrauterine Growth ◽  
Leucine Oxidation ◽  
Fetal Plasma ◽  
Oxidation Rates

Overcoming impaired growth in an intrauterine growth-restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We subjected fetal sheep to chronic placental insufficiency and tested whether prolonged amino acid infusion would increase protein accretion in these IUGR fetuses. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg−1·day−1 (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in the IUGR-AA than IUGR-Sal group ( P < 0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were fourfold higher in the IUGR-AA group ( P < 0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus the total amino acid delivery rate (net umbilical amino acid uptake + infusion rate) was higher in the IUGR-AA than IUGR-Sal group (30 ± 4 vs. 19 ± 1 μmol·kg−1·min−1, P < 0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate, measured using a leucine tracer, was higher in the IUGR-AA than IUGR-Sal group (2.5 ± 0.3 vs. 1.7 ± 0.3 μmol·kg−1·min−1, P < 0.05). Fetal protein accretion rate was not statistically different between the IUGR groups (1.6 ± 0.4 and 0.8 ± 0.3 μmol·kg−1·min−1 in IUGR-AA and IUGR-Sal, respectively) due to variability in response to amino acids. Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.

Removal of infused amino acids by splanchnic and leg tissues in humans

1986 ◽  
Vol 250 (4) ◽  
pp. E407-E413 ◽  
Author(s):  
R. A. Gelfand ◽  
M. G. Glickman ◽  
R. Jacob ◽  
R. S. Sherwin ◽  
R. A. DeFronzo
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Branched Chain Amino Acids ◽  
Acid Uptake ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Significant Uptake ◽  
Branched Chain

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.

Insulin stimulates branched chain amino acid uptake and diminishes nitrogen flux from skeletal muscle of injured patients

1986 ◽  
Vol 40 (4) ◽  
pp. 395-405 ◽  
Author(s):  
David C. Brooks ◽  
Palmer Q. Bessey ◽  
Preston R. Black ◽  
Thomas T. Aoki ◽  
Douglas W. Wilmore
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Nitrogen Flux ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Injured Patients

scholarly journals Global Regulatory Mutations in csrA andrpoS Cause Severe Central Carbon Stress in Escherichia coli in the Presence of Acetate

2000 ◽  
Vol 182 (6) ◽  
pp. 1632-1640 ◽  
Author(s):  
Bangdong Wei ◽  
Sooan Shin ◽  
David LaPorte ◽  
Alan J. Wolfe ◽  
Tony Romeo
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Rna Binding ◽  
Isocitrate Lyase ◽  
Tca Cycle ◽  
Amino Acid Uptake ◽  
Acetate Metabolism ◽  
Acid Uptake ◽  
Central Carbon ◽  
Glycogen Biosynthesis

ABSTRACT The csrA gene encodes a small RNA-binding protein, which acts as a global regulator in Escherichia coli and other bacteria (T. Romeo, Mol. Microbiol. 29:1321–1330, 1998). Its key regulatory role in central carbon metabolism, both as an activator of glycolysis and as a potent repressor of glycogen biosynthesis and gluconeogenesis, prompted us to examine the involvement ofcsrA in acetate metabolism and the tricarboxylic acid (TCA) cycle. We found that growth of csrA rpoS mutant strains was very poor on acetate as a sole carbon source. Surprisingly, growth also was inhibited specifically by the addition of modest amounts of acetate to rich media (e.g., tryptone broth). Cultures grown in the presence of ≥25 mM acetate consisted substantially of glycogen biosynthesis (glg) mutants, which were no longer inhibited by acetate. Several classes of glgmutations were mapped to known and novel loci. Several hypotheses were examined to provide further insight into the effects of acetate on growth and metabolism in these strains. We determined thatcsrA positively regulates acs(acetyl-coenzyme A synthetase; Acs) expression and isocitrate lyase activity without affecting key TCA cycle enzymes or phosphotransacetylase. TCA cycle intermediates or pyruvate, but not glucose, galactose, or glycerol, restored growth and prevented theglg mutations in the presence of acetate. Furthermore, amino acid uptake was inhibited by acetate specifically in thecsrA rpoS strain. We conclude that central carbon flux imbalance, inhibition of amino acid uptake, and a deficiency in acetate metabolism apparently are combined to cause metabolic stress by depleting the TCA cycle.

Amino acid metabolism by hepatocytes in a hybrid liver support bioreactor

1994 ◽  
Vol 17 (12) ◽  
pp. 663-669 ◽  
Author(s):  
M. Fuchs ◽  
J. Gerlach ◽  
J. Encke ◽  
J. Unger ◽  
M. Smith ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Metabolism ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Liver Support ◽  
Volume Increase ◽  
Liver Support System ◽  
Amino Acid Turnover ◽  
Acid Release ◽  
Branched Chain

The amino acid patterns of medium perfusate in a liver cell bioreactor developed for a hybrid liver support system have been measured. There were considerable changes in the concentrations of glutamic acid, glutamine, alanine, arginine, ornithine and branched chain amino acids during the first 10 days which is indicative of dynamic cellular metabolism. From day 15, steady state conditions of nitrogen metabolism are reflected by stable amino acid turnover. Monitoring of urea, K+, and P-450 activity suggests that hepatocytes have switched to a stable protein synthesis with a general amino acid uptake and keto acid release following cell volume increase

scholarly journals Influence of excess branched-chain amino acid uptake by Streptococcus mutans in human host cells

2017 ◽  
Vol 365 (3) ◽  
Author(s):  
Takafumi Arimoto ◽  
Rei Yambe ◽  
Hirobumi Morisaki ◽  
Haruka Umezawa ◽  
Hideo Kataoka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Streptococcus Mutans ◽  
Amino Acid Uptake ◽  
Host Cells ◽  
Acid Uptake ◽  
Human Host ◽  
Branched Chain Amino Acid ◽  
Branched Chain

scholarly journals Branched Chain Amino Acid Uptake and Muscle Free Amino Acid Concentrations Predict Postoperative Muscle Nitrogen Balance

1986 ◽  
Vol 204 (5) ◽  
pp. 513-523 ◽  
Author(s):  
DANIEL J. JOHNSON ◽  
ZHU-MING JIANG ◽  
MICHAEL COLPOYS ◽  
C. RAJA KAPADIA ◽  
ROBERT J. SMITH ◽  
...  
Keyword(s):  
Amino Acid ◽  
Free Amino Acid ◽  
Nitrogen Balance ◽  
Free Amino ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Amino Acid Concentrations

scholarly journals Inflammation and ER Stress Regulate Branched-Chain Amino Acid Uptake and Metabolism in Adipocytes

2015 ◽  
Vol 29 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Joel S. Burrill ◽  
Eric K. Long ◽  
Brian Reilly ◽  
Yingfeng Deng ◽  
Ian M. Armitage ◽  
...  
Keyword(s):  
Amino Acid ◽  
Er Stress ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Uptake And Metabolism

scholarly journals BCKDK regulates the TCA cycle through PDC to ensure embryonic development in the absence of PDK family

2020 ◽  
Author(s):  
Lia Heinemann-Yerushalmi ◽  
Lital Bentovim ◽  
Neta Felsenthal ◽  
Ron Carmel Vinestock ◽  
Nofar Michaeli ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Tca Cycle ◽  
Bioinformatic Analysis ◽  
Compensatory Mechanism ◽  
The Tca Cycle ◽  
Early Embryonic Lethality ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

AbstractPyruvate dehydrogenase kinases (PDK1-4) inhibit the TCA cycle by phosphorylating pyruvate dehydrogenase complex (PDC). Here, we show that the PDK family is dispensable for the survival of murine embryonic development and that BCKDK serves as a compensatory mechanism by inactivating PDC.First, we knocked out all fourPdkgenes one by one. Surprisingly,Pdktotal KO embryos developed and were born in expected ratios, but died by postnatal day 4 due to hypoglycemia or ketoacidosis.Finding that PDC was phosphorylated in these embryos suggested that another kinase compensates for the PDK family. Bioinformatic analysis implicated brunch chain ketoacid dehydrogenase kinase (Bckdk), a key regulator of branched chain amino acids (BCAA) catabolism. Indeed, knockout ofBckdkand thePdkfamily led to loss of PDC phosphorylation, increment in PDC activity, elevation of Pyruvate flux into the TCA and early embryonic lethality. These findings reveal a new regulatory crosstalk hardwiring BCAA and glucose catabolic pathways, which feed the TCA cycle.

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