Ovine fetal leucine kinetics and protein metabolism during decreased oxygen availability

1998 ◽  
Vol 274 (4) ◽  
pp. E618-E626 ◽  
Author(s):  
J. Ross Milley
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Fetal Growth ◽  
Oxygen Availability ◽  
Energy Needs ◽  
Leucine Kinetics ◽  
Metabolic Costs ◽  
Pool Model ◽  
Ovine Fetal ◽  
Maternal Hypoxia

The fetus depends on an uninterrupted supply of oxygen to provide energy, not only for basal metabolism but also for the metabolic costs of growth. By curtailing the metabolically expensive processes of protein turnover, the fetus could conserve energy when oxygen availability is limited. Therefore, this investigation was performed to find whether protein synthesis and breakdown are diminished during decreased fetal oxygen availability. Furthermore, if these conditions reduce fetal growth, protein synthesis should be affected more than breakdown so that protein accretion, an important component of fetal growth, also falls. In eight chronically prepared fetal lambs, we compared leucine kinetics (reciprocal pool model) during control conditions with measurements made during maternal hypoxia, a condition that limits fetal oxygen availability. Decreased fetal oxygen availability (−43%; P < 0.001) reduced fetal oxygen consumption (−16%; P < 0.01), as well as both the uptake of leucine across the placenta (−48%; P < 0.001) and its rate of decarboxylation (−30%; P < 0.001). Fetal protein synthesis decreased (−32%; P < 0.001) to a greater extent than proteolysis (−22%; P < 0.001). Consequently, fetal protein accretion, an important component of fetal growth, also decreased (−62%; P < 0.001). We calculate that the reduction in fetal protein synthesis and breakdown, both processes that require intracellular expenditure of ATP, decreased fetal energy needs sufficiently to account for most, if not all, of the decrease measured in fetal oxygen consumption.

Ovine fetal metabolism during norepinephrine infusion

1997 ◽  
Vol 273 (2) ◽  
pp. E336-E347 ◽  
Author(s):  
J. R. Milley
Keyword(s):  
Protein Synthesis ◽  
Fetal Growth ◽  
Oxidative Metabolism ◽  
Protein Metabolism ◽  
Amino Nitrogen ◽  
Fetal Life ◽  
Norepinephrine Infusion ◽  
Response To Stress ◽  
Endogenous Substrates ◽  
Ovine Fetal

Although stress in fetal life not only increases fetal catecholamine concentration but also decreases fetal growth, there have been few studies that define the specific role of catecholamines in mediating the fetal response to stress. None, however, have investigated effects on fetal amino acid or protein metabolism, processes that should be affected during aberrant fetal growth. Therefore, hormone concentrations as well as oxygen, glucose, lactate, and amino nitrogen, leucine, and protein metabolism were measured with and without norepinephrine infusion in fetuses of eight pregnant ewes (118-125 days of gestation). Transumbilical uptake of oxygen increased during norepinephrine infusion, whereas uptake of glucose remained constant and that of lactate and amino acids fell. The proportion of fetal oxidative metabolism that could be supported by transplacental uptake of exogenous substrates was < 1, indicating that endogenous substrates were used to maintain fetal oxidative metabolism and therefore that fetal growth was diminished. Both fetal leucine uptake and oxidation decreased during norepinephrine infusion, as did fetal protein synthesis and proteolysis. Fetal protein synthesis fell more than proteolysis, however. Consequently, fetal protein accretion, a variable closely related to fetal growth, also fell. Thus the effects of norepinephrine infusion in fetuses suggest that fetal catecholamines play an important role not only in altering fetal metabolism but also in regulating fetal growth.

Influence of protein intake on whole body and splanchnic leucine kinetics in humans

1997 ◽  
Vol 272 (4) ◽  
pp. E584-E591 ◽  
Author(s):  
M. Cayol ◽  
Y. Boirie ◽  
F. Rambourdin ◽  
J. Prugnaud ◽  
P. Gachon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Intake ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Body ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Protein X ◽  
Pool Model

The influence of the protein content of the meal on protein turnover was investigated in the splanchnic bed and in the remaining parts of the body in humans. Two groups of five subjects consumed every 20 min a liquid formula providing either 1.5 g protein x kg(-1) x day(-1) (P) or no protein (PF). L-[1-(13)C]leucine and L-[5,5,5-(2)H3]leucine were administered by vein and gut, respectively. An open two-pool model was developed to calculate leucine kinetics in both compartments, with the assumption that the enrichment of the tracers incorporated into very low density lipoprotein apolipoprotein B100 at isotopic steady state could reflect the leucine labeling in the splanchnic region. Nonsplanchnic uptake and release of leucine were not significantly different in the two groups. Within the splanchnic area, leucine uptake was 2.1 times higher in the P than in the PF group (P < 0.01), whereas leucine release was reduced but not significantly (-19%) in the P group compared with the PF group. Moreover, data derived from this model showed that protein intake induced an increase in whole body protein synthesis and no change in whole body protein breakdown. Albumin synthesis, as well as its contribution to whole body protein synthesis, was significantly enhanced by protein intake.

Effects of increased cortisol concentration on ovine fetal leucine kinetics and protein metabolism

1995 ◽  
Vol 268 (6) ◽  
pp. E1114-E1122 ◽  
Author(s):  
J. R. Milley
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Plasma Cortisol ◽  
Cortisol Concentration ◽  
Late Gestation ◽  
Fetal Plasma ◽  
Plasma Cortisol Concentration ◽  
Arterial Blood ◽  
Leucine Kinetics ◽  
Ovine Fetal

Fetal protein accretion decreases as gestation progresses, primarily because protein synthesis decreases. Also, glucocorticoid primarily because protein synthesis decreases. Also, glucocorticoid concentrations increase late in gestation, and restraint of growth is one of the most consistently noted effects of glucocorticoids. Therefore, this study was done to determine whether fetal protein accretion is decreased by increased cortisol concentration and whether such an effect might be due to decreased protein synthesis or increased proteolysis. Six days after surgery, fetal leucine and protein metabolism was measured in eight pregnant ewes (114-119 days of gestation) at normal and elevated cortisol concentrations. Arterial blood leucine concentration, fetal leucine disposal rate, and exogenous leucine uptake were unaffected by cortisol infusion. Fetal leucine decarboxylation, however, increased by 19% (P < 0.001). Increased fetal cortisol concentration increased fetal proteolysis by 11% (P < 0.001) but did not affect the use of leucine for protein synthesis. Consequently, fetal protein accretion fell by 34% (P < 0.002). We conclude that increased fetal plasma cortisol concentration increases fetal proteolysis, thereby decreasing the rate of fetal protein accretion, an effect different from the decreased protein synthesis reported in late gestation.

Ovine fetal leucine kinetics and protein metabolism during acute metabolic acidosis

1997 ◽  
Vol 272 (2) ◽  
pp. E275-E281
Author(s):  
J. R. Milley
Keyword(s):  
Amino Acids ◽  
Metabolic Acidosis ◽  
Fetal Growth ◽  
Protein Metabolism ◽  
Protein Breakdown ◽  
Leucine Uptake ◽  
Leucine Kinetics ◽  
Acute Metabolic Acidosis ◽  
Ovine Fetal ◽  
Fetal Acidosis

Fetal acidosis is associated with poor fetal growth. Because protein accretion is an important component of fetal growth, we used seven chronically prepared fetal lambs (10-16 days postoperation) to find whether fetal metabolic acidosis affected fetal protein accretion, and, if so, whether such effects were due to decreased synthesis or increased breakdown of proteins. Fetal leucine kinetics were measured during infusion of [1-(14)C]leucine by the reciprocal pool method. After control measurements, metabolic acidosis was induced by fetal infusion of 0.5 N HCl, and the measurements were repeated. Although fetal leucine concentration rose (164 +/- 11 vs. 216 +/- 15 microM; P < 0.001), fetal leucine uptake fell during acidosis (3.33 +/- 0.30 vs. 1.43 +/- 0.35 micromol x kg(-1) x min(-1); P < 0.05). However, the influx of leucine from protein breakdown increased (12.6 +/- 2.6 vs. 14.7 +/- 2.6 micromol x kg(-1) x min(-1); P < 0.02). The incorporation of leucine into fetal protein was unaffected by acidosis, so that fetal protein accretion fell (0.48 +/- 1.04 vs. -2.32 +/- 1.53 micromol x kg(-1) x min(-1); P < 0.001). Fetal leucine decarboxylation increased during acidosis (2.85 +/- 0.33 vs. 3.75 +/- 0.61 micromol x kg(-1) x min(-1); P < 0.05). We conclude that fetal metabolic acidosis stimulates pathways to degrade both protein and at least one of the subsequently derived amino acids, leucine. The consequence of such changes induced by acidosis is decreased protein accretion, a finding incompatible with normal fetal growth.

Metabolism during normoxia, hyperoxia, and recovery in newborn rats

1992 ◽  
Vol 70 (3) ◽  
pp. 408-411 ◽  
Author(s):  
Peter B. Frappell ◽  
Andrea Dotta ◽  
Jacopo P. Mortola
Keyword(s):  
Carbon Dioxide ◽  
Oxygen Consumption ◽  
Metabolic Rate ◽  
Carbon Dioxide Production ◽  
Oxygen Availability ◽  
Aerobic Metabolism ◽  
Newborn Rats ◽  
Ambient Temperatures ◽  
Positive Effects

Aerobic metabolism (oxygen consumption, [Formula: see text], and carbon dioxide production, [Formula: see text]) has been measured in newborn rats at 2 days of age during normoxia, 30 min of hyperoxia (100% O2) and an additional 30 min of recovery in normoxia at ambient temperatures of 35 °C (thermoneutrality) or 30 °C. In normoxia, at 30 °C [Formula: see text] was higher than at 35 °C. With hyperoxia, [Formula: see text] increased in all cases, but more so at 30 °C (+20%) than at 35 °C (+9%). Upon return to normoxia, metabolism readily returned to the prehyperoxic value. The results support the concept that the normoxic metabolic rate of the newborn can be limited by the availability of oxygen. At temperatures below thermoneutrality the higher metabolic needs aggravate the limitation in oxygen availability, and the positive effects of hyperoxia on [Formula: see text] are therefore more apparent.Key words: neonatal respiration, oxygen consumption, thermoregulation.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (5) ◽  
pp. 381-386 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In constrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

Oxygen Availability as a Control Factor in the Density-Dependent Regulation of Protein Synthesis in Cell Culture

1974 ◽  
Vol 14 (2) ◽  
pp. 331-337
Author(s):  
DESH PAL S. VERMA ◽  
A. MARCUS
Keyword(s):  
Cell Culture ◽  
Protein Synthesis ◽  
Respiratory Rate ◽  
Initial Function ◽  
Fold Increase ◽  
Oxygen Availability ◽  
Control Factor ◽  
Atp Level ◽  
Density Dependent ◽  
Inadequate Nutrition

Dilution of a density-inhibited Arachis culture results in a 10-fold increase in capacity for protein synthesis during the first 2 h after dilution. The limitation in the density-inhibited state is not inadequate nutrition, inappropriate pH, or a diffusible inhibitor as the dilution can be carried out in medium obtained by filtration of 14-day cells. The respiratory rate of the culture increases 2-fold immediately after dilution and the ATP level increases 3-fold dunng the 2-h period subsequent to dilution. These observations suggest that the initial function activated by dilution is an increased availability of oxygen and that this increase in oxygen provides an increased level of ATP, finally resulting in an increased rate of protein synthesis. This idea is further supported by the finding that both the increase in cellular ATP and the acceleration of the rate of protein synthesis can be obtained in dense culture, in the absence of dilution, by maintaining the cells for 2 h under oxygen.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (2) ◽  
pp. 109-114 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

Action of adenosine on energetics, protein synthesis and K(+) homeostasis in teleost hepatocytes

2000 ◽  
Vol 203 (17) ◽  
pp. 2657-2665 ◽  
Author(s):  
G. Krumschnabel ◽  
C. Biasi ◽  
W. Wieser
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Atpase Activity ◽  
Oncorhynchus Mykiss ◽  
Carassius Auratus ◽  
Goldfish Carassius Auratus ◽  
Inhibition Of Protein Synthesis ◽  
Rate Of Oxygen Consumption ◽  
A1 Receptor ◽  
Lactate Formation

In a comparative study, we analysed the effects of adenosine on the energetics, protein synthesis and K(+)homeostasis of hepatocytes from the anoxia-tolerant goldfish Carassius auratus and the anoxia-intolerant trout Oncorhynchus mykiss. The rate of oxygen consumption did not respond immediately to the addition of adenosine to the cells from either species, but showed a significant decrease in trout hepatocytes after 30 min. The anaerobic rate of lactate formation was not significantly affected by adenosine in goldfish hepatocytes, but was increased in trout cells. We also studied the effects of adenosine on the two most prominent ATP consumers in these cells, protein synthesis and Na(+)/K(+)-ATPase activity. Under aerobic conditions, adenosine inhibited protein synthesis of hepatocytes from goldfish by 51% and of hepatocytes from trout by 32%. During anoxia, the rate of protein synthesis decreased by approximately 50% in goldfish hepatocytes and by 90% in trout hepatocytes, and this decrease was not altered by the presence of adenosine. Adenosine inhibited normoxic Na(+)/K(+)-ATPase activity and K(+)efflux by 20–35% in the cells of both species. An investigation into the mechanism underlying the inhibition of protein synthesis by adenosine indicated that, in the goldfish cells, adenosine acts via a membrane receptor-mediated pathway, i.e. the effect of adenosine was abolished by applying the A1 receptor antagonist 8-phenyltheophylline. In the trout, however, the uptake of adenosine into hepatocytes seems to be required for an effect on protein synthesis. [Ca(2+)](i) does not seem to be involved in the inhibition of protein synthesis by adenosine.

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