scholarly journals THE PLACENTA AND PROTEIN METABOLISM

1955 ◽  
Vol 101 (6) ◽  
pp. 617-626 ◽  
Author(s):  
G. H. Whipple ◽  
R. B. Hill ◽  
R. Terry ◽  
F. V. Lucas ◽  
C. L. Yuile
Keyword(s):  
Amino Acids ◽  
Oral Administration ◽  
Plasma Protein ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Maternal Plasma ◽  
Blue Dye ◽  
Placental Function ◽  
Length Of Gestation

Plasma proteins tagged in vivo by feeding D-L-lysine-ϵ-C14 to donor dogs have been administered to pregnant dogs by both oral and intravenous routes. A relatively small percentage of the C14 activity originally incorporated in these proteins is found to pass from mother to fetus after intravenous injection. The amount transferred tends to increase with the length of gestation period and total number of fetuses. Plasma protein labeled with I131 does not cross the placenta in the dog, but does in the rabbit. Evans blue dye does not cross the placenta of the dog. After oral administration of labeled plasma protein or lysine, C14 is transferred promptly and in considerable quantity to the fetus. Labeled plasma proteins disappear more rapidly from the circulation of pregnant than of normal dogs. This increased metabolic turnover occurs without excretion of any excess waste metabolites. The chorionic epithelium, gram for gram, is probably 2 to 3 times as active as the hepatic epithelium in protein metabolism. These findings indicate an important placental function related to maternal and fetal protein metabolism. While the placenta utilizes maternal plasma proteins and amino acids, in a quantitative sense the latter appear to supply the major nitrogen needs of the growing fetus.

scholarly journals Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis

1975 ◽  
Vol 146 (1) ◽  
pp. 141-155 ◽  
Author(s):  
K N Jeejeebhoy ◽  
J Ho ◽  
G R Greenberg ◽  
M J Phillips ◽  
A Bruce-Robertson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Plasma Protein ◽  
Plasma Proteins ◽  
Horse Serum ◽  
Rat Hepatocyte ◽  
Isolated Rat

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.

scholarly journals Effects of the hepatotoxic agents retrorsine and aflatoxin B1 on hepatic protein synthesis in the rat

1968 ◽  
Vol 109 (1) ◽  
pp. 87-91 ◽  
Author(s):  
S. Villa-Treviño ◽  
D. D. Leaver
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Rat Liver ◽  
Aflatoxin B1 ◽  
Plasma Proteins ◽  
Pyrrolizidine Alkaloid ◽  
Main Site ◽  
Nuclear Rna ◽  
Hepatic Protein Synthesis

1. Aflatoxin and the pyrrolizidine alkaloid retrorsine inhibited the incorporation of labelled amino acids into rat liver and plasma proteins in vivo. Inhibition was greater and detected earlier with retrorsine (1hr.) than with aflatoxin (3hr.). 2. Both toxins affected the liver ribosomal aggregates, causing increases in the proportion of monomers plus dimers. The effect of retrorsine was greater than that of aflatoxin. 3. Incorporation of labelled amino acids into proteins of cell-free preparations of liver from rats treated with aflatoxin was lower than in control preparations. The main site of inhibition appeared to be the ribosomes. 4. Both toxins inhibited the incorporation of orotate into liver nuclear RNA 1hr. after administration.

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans

1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.

scholarly journals A plasma protein fractionation procedure for use in studies of protein metabolism. Its application to the measurement of synthesis rates of two α1-glycoproteins and other serum proteins in the rat

1974 ◽  
Vol 141 (3) ◽  
pp. 655-665 ◽  
Author(s):  
J. Ho ◽  
K. N. Jeejeebhoy ◽  
R. H. Painter
Keyword(s):  
Electrophoretic Mobility ◽  
Plasma Protein ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Serum Proteins ◽  
Single Sample ◽  
Protein Fractionation ◽  
Step Method ◽  
Preparative Scale ◽  
Fractionation Procedure

A two-step method for the separation of five different plasma proteins on a preparative scale, which is capable of being extended to allow the separation of other plasma proteins, is described. The proteins separated were fibrinogen, two α1-glycoproteins, albumin and transferrin. The α1-glycoproteins were characterized in terms of electrophoretic mobility, ultracentrifugal and immunological characteristics. By using this method, it was shown that a single sample of plasma could be fractionated to yield purified proteins in sufficient quantity to simultaneously measure the synthesis of the two α1-glycoproteins, albumin and transferrin in the rat with McFarlane's technique (McFarlane, 1963; Reeve et al., 1963; McFarlane et al., 1965).

An in vivo study of ovine placental transport of essential amino acids

2001 ◽  
Vol 280 (1) ◽  
pp. E31-E39 ◽  
Author(s):  
Cinzia L. Paolini ◽  
Giacomo Meschia ◽  
Paul V. Fennessey ◽  
Adrian W. Pike ◽  
Cecilia Teng ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Concentration ◽  
Essential Amino Acids ◽  
Maternal Plasma ◽  
Transport Systems ◽  
Fetal Plasma ◽  
Placental Transport ◽  
Rate Limiting ◽  
Pulse Flux

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes. Measurements of concentration and molar enrichment in maternal and fetal plasma and of umbilical plasma flow were used to calculate the ratio of transplacental pulse flux to maternal concentration (clearance) for each EA. Five EA (Met, Phe, Leu, Ile, and Val) had relatively high and similar clearances and were followed, in order of decreasing clearance, by Trp, Thr, His, and Lys. The five high-clearance EA showed strong correlation ( r 2 = 0.98) between the pulse flux and maternal concentration. The study suggests that five of the nine EA have similar affinity for a rate-limiting placental transport system that mediates rapid flux from mother to fetus, and that differences in transport rates within this group of EA are determined primarily by differences in maternal plasma concentration.

scholarly journals Effect of hypophysectomy on the rates of protein synthesis and degradation in rat liver

1979 ◽  
Vol 178 (3) ◽  
pp. 725-731 ◽  
Author(s):  
R D Conde
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Rat Liver ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Degradation Rates ◽  
Hypophysectomized Rats ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

The effect of hypophysectomy on the protein metabolism of the liver in vivo was studied. Fractional rates of protein synthesis and degradation were determined in the livers of normal and hypophysectomized rats. Synthesis was measured after the injection of massive amounts of radioactive leucine. Degradation was estimated either as the balance between synthesis and accumulation of stable liver proteins or from the disappearance of radioactivity from the proteins previously labelled by the injection of NaH14CO3. The results indicate that: (1) hypophysectomy diminishes the capacity of the liver to synthesize proteins in vivo, mainly of those that are exported as plasma proteins; (2) livers of both normal and hypophysectomized rats show identical protein-degradation rates, whereas plasma proteins are degraded slowly after hypophysectomy.

scholarly journals PLASMA PROTEIN METABOLISM—NORMAL AND ASSOCIATED WITH SHOCK

1944 ◽  
Vol 80 (6) ◽  
pp. 455-475 ◽  
Author(s):  
R. M. Fink ◽  
T. Enns ◽  
C. P. Kimball ◽  
H. E. Silberstein ◽  
W. F. Bale ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Blood Stream ◽  
Dilution Curve ◽  
Body Protein ◽  
Protein Mass ◽  
Rapid Exchange ◽  
Isotope Concentration ◽  
Heavy Nitrogen

Labeled plasma proteins are produced by administering to dogs the amino acid lysine synthesized with heavy nitrogen. Such labeled proteins are apparently indistinguishable biologically from proteins of normal isotope concentration. Labeled plasma proteins, as plasma, injected into normal dogs pass out of the blood stream at an initially rapid but constantly decreasing non-logarithmic rate. This outflow is balanced by a simultaneous inflow of plasma proteins from the tissues. Fifty per cent of the labeled protein is out of the blood stream in about 24 hours; 75 per cent in about 6 days. Shock due to trauma of intestine or leg shows a dilution curve of labeled plasma protein not unlike that of the normal dog. If anything, dilution appears a little less rapid in shock. Since the usual shrinkage of plasma volume and plasma protein mass is present in these shocked dogs, these data are compatible with a decreased inflow of protein into the plasma during shock. Methods are described which are suitable for the use of heavy nitrogen incorporated in the epsilon group of lysine and its subsequent analysis in body fluids. These data may indicate that the plasma proteins are normally in constant and rapid exchange with a mobile pool of body protein.

Morphiceptin analogs as potential analgesic and anti-diarrheal agents

2019 ◽  
Vol 6 ◽  
pp. 11-20
Author(s):  
Katarzyna Gach-Janczak ◽  
Anna Janeck
Keyword(s):  
Amino Acids ◽  
Oral Administration ◽  
Pain Sensitivity ◽  
Proteolytic Enzymes ◽  
Antinociceptive Effect ◽  
Opioid Peptide ◽  
Artificial Membrane ◽  
Selective Ligand ◽  
Reduction Of Pain

Morphiceptin (Tyr-Pro-Phe-Pro-NH<sub>2</sub>) – an opioid peptide, originating from enzymatic degradation of milk protein, β-casein, is a selective ligand μ-opioid receptors. These receptors play a an important role in reduction of pain sensitivity and in the regulation of the functions of many systems, including the gastrointestinal tract. Due to the rapid degradation by proteolytic enzymes and low bioavailability, morphiceptin can not be used as a medicine. The aim of the project was the synthesis and evaluation of the pharmacological profile of novel morphiceptin analogs, in search of compounds with a strong analgesic and anti-diarrheal activity, which acted only peripherally and are active after oral administration. We synthesized five series of morphiceptin analogs. The most interesting turned out compounds modified with the use of β-amino acids. Modification of morphiceptin at positions 2 or 3 by introduction of β<sup>2</sup>- or β<sup>3</sup>-amino acids and additionally in position 1 by replacing Tyr by Dmt (2’,6’-dimethyltyrosine), resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles. An analog of the sequence Dmt-D-Ala-(R)-β<sup>2</sup>-1-Nal-Pro-NH<sub>2</sub) [Nal= 3-(1-naphthyl)-alanine] was selected for <i>in vivo</i> experiments in mice. This peptide showed a strong antinociceptive effect (peripheral analgesic) and antidiarrheal activity (comparable to loperamide) after intraperitoneal as well as oral administration. The PAMPA test, showed that this compound did not cross the artificial membrane imitating the blood-brain barrier and therefore its action should be only peripheral. The new analog may become an interesting lead compound in the development of peripherally restricted drugs for the treatment of gastrointestinal disorders.

Effect of insulin-induced hypoglycemia on protein metabolism in vivo.

1990 ◽  
Vol 259 (3) ◽  
pp. E342 ◽  
Author(s):  
H Hourani ◽  
P Williams ◽  
J A Morris ◽  
M E May ◽  
N N Abumrad
Keyword(s):  
Amino Acids ◽  
Protein Metabolism ◽  
Conscious Dogs ◽  
Major Contributor ◽  
Leucine Kinetics ◽  
Significant Change ◽  
Plasma Leucine ◽  
Net Release ◽  
Oxidative Rate

The effects of insulin-induced hypoglycemia (IIH) on leucine kinetics (mumol.kg-1.min-1) and interorgan flow of amino acids (AA) were examined in 2 groups of 18-h fasted conscious dogs. Insulin was infused at 5 mU.kg-1.min-1 for 3 h. IIH (40 +/- 5 mg/dl) resulted in a drop in plasma leucine (114 +/- 10 to 64 +/- 9 microM) and leucine rate of appearance (Ra) (3.1 +/- 0.1 to 2.4 +/- 0.2) within 1 h but gradually increased (P less than 0.05) to 145 +/- 30 microM and 3.8 +/- 0.5 by 3 h. Leucine oxidative rate of disposal (Rd) increased from 0.44 +/- 0.08 to 1.02 +/- 0.35 (P less than 0.01), and nonoxidative Rd dropped initially but was near basal levels by 3 h. When euglycemia was maintained, there was sustained drop in plasma leucine from 122 +/- 12 to 42 +/- 6 mumol/l, leucine Ra from 3.1 +/- 0.4 to 1.8 +/- 0.2, oxidative Rd from 0.36 +/- 0.03 to 0.22 +/- 0.04, and nonoxidative Rd from 2.75 +/- 0.4 to 1.6 +/- 0.2 (all P less than 0.01). IIH was associated with a significant net release of leucine (and other AA) across the gut (0.04 +/- 0.05 to 1.86 +/- 0.30 mumol.kg-1.min-1; P less than 0.05). In the group with euglycemia there was no significant change in the gut balance of leucine. We conclude that IIH is associated with a proteolytic response and that the gut is the major contributor to this response.

scholarly journals Simplified Analytical Methods for the Measurement of the Synthesis Rate of Plasma Proteins in Vivo by the [14C]Carbonate Method

1984 ◽  
Vol 21 (5) ◽  
pp. 378-386
Author(s):  
S Caine ◽  
A Fleck
Keyword(s):  
Mass Spectrometry ◽  
Plasma Protein ◽  
Analytical Methods ◽  
Plasma Proteins ◽  
Specific Activity ◽  
Synthesis Rate ◽  
Original Procedure

We describe a method for obtaining the specific activity of 14C in urea, essential in the measurement of the synthesis rate of a plasma protein in vivo, which is simpler than the original procedure. The principle is the measurement of 14CO2 and NH4+ separately, after incubation with urease. A simple alteration gives samples of 13CO2 for mass spectrometry. The ‘recoveries’ of 14C and 13C in urea were invariably between 90 and 96% and the CV was 3%.

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