scholarly journals The contribution of phenylalanine to tyrosine metabolism in vivo. Studies in the post-absorptive and phenylalanine-loaded rat

1983 ◽  
Vol 210 (3) ◽  
pp. 811-817 ◽  
Author(s):  
L L Moldawer ◽  
I Kawamura ◽  
B R Bistrian ◽  
G L Blackburn
Keyword(s):  
In Vivo Studies ◽  
Whole Body ◽  
Constant Infusion ◽  
Substantial Contribution ◽  
Oxidation Rates ◽  
Plasma Phenylalanine ◽  
Tyrosine Oxidation ◽  
Tyrosine Metabolism ◽  
Plasma Tyrosine

1. Rates of appearance and oxidation of plasma L-leucine, L-phenylalanine and L-tyrosine, as well as conversion of plasma phenylalanine into plasma tyrosine, were determined in 90-120 g rats after overnight starvation and while receiving 115-120 mumol of L-phenylalanine/h. 2. In the post-absorptive state, plasma tyrosine and phenylalanine appearances were similar, despite the fact that 22% of plasma tyrosine appearance could be attributed to the hydroxylation of phenylalanine. 3. A constant infusion of 115-120 mumol of L-phenylalanine/h did not significantly alter plasma leucine kinetics, but increased appearance of plasma phenylalanine and tyrosine. The percentage of phenylalanine and tyrosine appearance that was oxidized increased from 12.1% and 24.4% to 37.3% and 48.0% respectively. In phenylalanine-loaded rats, 72% of plasma tyrosine appearance could be attributed to the conversion of phenylalanine. 4. Whole-body tyrosine oxidation measured from a continuous infusion of either L-[14C]tyrosine or L-[14C]phenylalanine differed by 165%. 5. It can be concluded that, in the post-absorptive state, phenylalanine hydroxylation makes a substantial contribution to the plasma appearance of tyrosine and is significantly increased when phenylalanine is administered. The disposal of excess infused phenylalanine is a result of a greater percentage of plasma phenylalanine being converted into tyrosine and a greater proportion of tyrosine being further oxidized. However, apparent tyrosine oxidation rates estimated from plasma tyrosine specific radioactivities and appearance of expired 14CO2 during administration of [14C]tyrosine are underestimates of true rates, in part because tyrosine generated from phenylalanine hydroxylation is catabolized without freely equilibrating with the plasma compartment.

Gastrointestinal tract, hepatic, hindlimb, and renal recovery of CO2 in vivo

2000 ◽  
Vol 89 (5) ◽  
pp. 2000-2006 ◽  
Author(s):  
Jennifer D. Gresham ◽  
Koji Okamura ◽  
Phillip E. Williams ◽  
Kareem Jabbour ◽  
Paul J. Flakoll
Keyword(s):  
Gastrointestinal Tract ◽  
Pool Size ◽  
In Vivo Studies ◽  
Whole Body ◽  
Constant Infusion ◽  
Potential Contribution ◽  
Experimental Conditions ◽  
Rate Of Decay ◽  
Total Body

Whole body oxidative rates of labeled substrates are often measured by collecting expired air and determining the amount of labeled CO2 that is produced. However, the CO2 produced may not be completely recovered under all circumstances, and there is a wide variation in values reported under different experimental conditions (∼50–100%). The potential contribution of specific organs to this variation has not been defined. In vivo studies using healthy, postabsorptive, multicatheterized conscious canines were conducted to determine gastrointestinal tract, hepatic, hindlimb, and renal recoveries of NaH14CO3 during a 180-min constant infusion [0.022 ± 0.002 (SE) μCi · kg−1 · min−1]. Before the constant infusion period, a bolus infusion of NaH14CO3 (1.76 ± 0.16 μCi/kg) was given, and the rate of decay in blood was measured over a 15-min period to determine pool size. The pool size for the distribution of14CO2 was ∼80% of the total body pool (16.0 ± 1.7 liters). Whole body recovery was 97.2 ± 6.7%. The recoveries across the liver, gut, leg, and kidney were 99.9 ± 1.3, 98.0 ± 1.4, 96.7 ± 2.6, and 99.9 ± 2.1%, respectively. In conclusion, hepatic, gastrointestinal tract, hindlimb, and renal recoveries of CO2 in vivo were near 100%, suggesting that CO2 loss is not greater in gluconeogenic organs and that corrections for incomplete recovery of CO2, when measuring oxidation of substrates across these organs under normal postabsorptive conditions, would be very minor.

scholarly journals Comparison of different techniques for estimating rates of protein synthesis in vivo in healthy and bacteraemic rats

1985 ◽  
Vol 226 (1) ◽  
pp. 37-42 ◽  
Author(s):  
J J Pomposelli ◽  
J D Palombo ◽  
K J Hamawy ◽  
B R Bistrian ◽  
G L Blackburn ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Rectus Muscle ◽  
Stochastic Modelling ◽  
Whole Body ◽  
Constant Infusion ◽  
Second Phase ◽  
Sprague Dawley ◽  
Body Protein ◽  
To Receive

Previous studies have reported that use of a flooding dose of radiolabelled amino acid is a more precise technique than the constant infusion of tracer quantities for determining rates of protein synthesis in rapidly turning-over tissues in the rat. However, there has been little direct investigation comparing different methods under comparable conditions. Initially, 12 healthy male Sprague-Dawley rats, weighing approx. 100 g, were randomized to receive either a bolus intravenous injection of 100 mumol of L-leucine (containing 30 microCi of [1-14C]leucine)/100 g body wt., or a continuous 2 h tracer infusion of [14C]leucine. In the second phase of the experiment, 12 additional rats were intravenously injected with 1 × 10(8) colony-forming units of Pseudomonas aeruginosa and 16 h later randomized to receive one of two infusions described above. Total protein synthesis as well as fractional synthesis rates were determined in liver, rectus muscle and whole body. Synthesis rates measured in liver, muscle and whole body were significantly higher in bacteraemic rats than in healthy rats. The flooding-dose methodology gave significantly higher estimates of protein synthesis in the liver, skeletal muscle and whole body than did the continuous-infusion method using direct measurement of the acid-soluble fraction from the respective tissue. Indirect estimates of whole-body protein synthesis based on plasma enrichments and stochastic modelling gave the lowest values.

Compartmental model of leucine kinetics in humans

1991 ◽  
Vol 261 (4) ◽  
pp. E539-E550 ◽  
Author(s):  
C. Cobelli ◽  
M. P. Saccomani ◽  
P. Tessari ◽  
G. Biolo ◽  
L. Luzi ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Compartmental Model ◽  
Linear Time ◽  
A Priori ◽  
Normal Subjects ◽  
Whole Body ◽  
Constant Infusion ◽  
Individual Subject ◽  
Domain Of Validity

The complexity of amino acid and protein metabolism has limited the development of comprehensive, accurate whole body kinetic models. For leucine, simplified approaches are in use to measure in vivo leucine fluxes, but their domain of validity is uncertain. We propose here a comprehensive compartmental model of the kinetics of leucine and alpha-ketoisocaproate (KIC) in humans. Data from a multiple-tracer administration were generated with a two-stage (I and II) experiment. Six normal subjects were studied. In experiment I, labeled leucine and KIC were simultaneously injected into plasma. Four plasma leucine and KIC tracer concentration curves and label in the expired CO2 were measured. In experiment II, labeled bicarbonate was injected into plasma, and labeled CO2 in the expired air was measured. Radioactive (L-[1-14C]leucine, [4,5-3H]KIC, [14C]bicarbonate) and stable isotope (L-[1-13C]leucine, [5,5,5-2H3]KIC, [13C]bicarbonate) tracers were employed. The input format was a bolus (impulse) dose in the radioactive case and a constant infusion in the stable isotope case. A number of physiologically based, linear time-invariant compartmental models were proposed and tested against the data. The model finally chosen for leucine-KIC kinetics has 10 compartments: 4 for leucine, 3 for KIC, and 3 for bicarbonate. The model is a priori uniquely identifiable, and its parameters were estimated with precision from the five curves of experiment I. The separate assessment of bicarbonate kinetics (experiment II) was shown to be unnecessary. The model defines masses and fluxes of leucine in the organism, in particular its intracellular appearance from protein breakdown, its oxidation, and its incorporation into proteins. An important feature of the model is its ability to estimate leucine oxidation by resolving the bicarbonate model in each individual subject. Finally, the model allows the assessment of the domain of validity of the simpler commonly used models.

L-[U-14C] Tyrosine Metabolism of the Perfused Cat Brain with High Plasma Phenylalanine or without Plasma Tyrosine

1970 ◽  
Vol 24 (4) ◽  
pp. 219-226
Author(s):  
Shosuke WATANABE ◽  
Katsusuke MITSUNOBU ◽  
Takanori SANNOMIYA ◽  
Saburo OTSUKI
Keyword(s):  
High Plasma ◽  
Plasma Phenylalanine ◽  
Cat Brain ◽  
Tyrosine Metabolism ◽  
Plasma Tyrosine

Altered lipid kinetics in adjuvant recombinant human growth hormone-treated multiple-trauma patients

1994 ◽  
Vol 267 (4) ◽  
pp. E560-E565 ◽  
Author(s):  
M. Jeevanandam ◽  
S. R. Petersen
Keyword(s):  
Growth Hormone ◽  
Multiple Trauma ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Whole Body ◽  
Constant Infusion ◽  
Control Group ◽  
Trauma Patients ◽  
Oxidation Rates

Adjuvant recombinant human growth hormone therapy during the postinjury period may improve the efficiency of utilization of body energy stores. In a group of 20 severely injured highly catabolic hypermetabolic adult multiple-trauma victims, we have investigated the basic lipid kinetics of trauma (study I) and its modification after 7 days of intravenous feeding (total parenteral nutrition) with (group H, n = 10) or without (group C, n = 10) daily rhGH (0.15 mg somatotropin.kg-1.day-1) intramuscular injections (study II). Whole body lipolysis rate (2-stage primed constant infusion of 10% glycerol), substrate net oxidation rates (indirect calorimetry), and plasma levels of hormones were determined. Compared with the control group (group C) the treatment group (group H) showed significantly (P = 0.006) enhanced rates of lipolysis and free fatty acid reesterification (10 +/- 2 to 18 +/- 2 kcal.kg-1.day-1, P = 0.05). As a function of resting energy expenditure (REE), a trend of increased net glucose oxidation [32 +/- 10 vs. 56 +/- 7% REE, not significant (NS)] and decreased fat (40 +/- 8 vs. 25 +/- 5% REE, NS) and protein oxidation rates (28 +/- 2 vs. 19 +/- 2% REE, P = 0.007) were also indicated. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements in injury.

Bcl-2 Family Protein Inhibitors Induce a Unique Thrombocytopenia In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4236-4236 ◽  
Author(s):  
Steven W. Elmore ◽  
Joy Bauch ◽  
Ryan M. Fryer ◽  
Laurie Iciek ◽  
Kennan Marsh ◽  
...  
Keyword(s):  
Tumor Regression ◽  
Underlying Mechanism ◽  
In Vivo Studies ◽  
Whole Body ◽  
Protein Inhibitors ◽  
Drug Induced ◽  
Post Dose ◽  
Platelet Counts ◽  
Family Protein

Abstract We recently disclosed the discovery of ABT-737, a potent antagonist of antiapoptotic Bcl-2 family proteins that induced tumor regression in murine xenograft models. ABT-263 is a related, orally bioavailable Bcl-2 family protein inhibitor that is currently in clinical development. For both agents, multiple daily dosing from two to four weeks was well tolerated in all species evaluated. The primary preclinical toxicological finding in mouse, rat and dog was a unique thrombocytopenia characterized by a rapid clearance of circulating platelets. A series of in vivo studies that were performed to better characterize this phenomenon are described here. After a single intravenous or oral dose in dogs, circulating platelet counts decreased rapidly and concentration dependently with a nadir at approximately six hours post administration. Platelet counts returned to near normal levels within several days post dose, accompanied by an increase in both mean platelet volume and percent of reticulated platelets. Analysis of platelets by aggregometry during this rebound period indicated that returning platelets were fully functional. Following multiple doses, platelet counts also decreased rapidly after initial dosing, but exhibited evidence of rebound during the dosing period that appeared to be dose dependant. Evaluation of fibrinogen, d-dimer, antithrombin-III, PT and APTT did not support a mechanism involving consumptive coagulopathy. Whole body scintography utilizing [111] Indium labeled platelets in dogs indicated that platelet clearance after compound administration is primarily mediated by the liver. These data suggest that ABT-737 and ABT-263 preferentially affect circulating platelets rather than abrogating platelet production in the bone marrow. In fact, the observed rebound in platelet count in the face of continued dosing reflects the capacity for the animals to compensate for the effect. The enantiomer of ABT-737 (which has significantly lower activity against Bcl-2 family proteins) had no effect on circulating platelets in animals suggesting an underlying mechanism that is dependent on inhibition of antiapoptotic Bcl-2 family proteins. The unusually rapid kinetics of platelet clearance and recovery suggests that the drug-induced thrombocytopenia elicited by these Bcl-2 family protein inhibitors is unique compared to that observed with conventional cytotoxic chemotherapy.

scholarly journals In vivo threonine oxidation in growing pigs fed on diets with graded levels of threonine

1996 ◽  
Vol 75 (6) ◽  
pp. 825-837 ◽  
Author(s):  
N. Le Floc'h ◽  
C. Obled ◽  
B. Sève
Keyword(s):  
Specific Radioactivity ◽  
Vena Cava ◽  
Live Weight ◽  
Growing Pigs ◽  
Whole Body ◽  
Constant Infusion ◽  
Balanced Diet ◽  
Liver And Pancreas ◽  
Venous Plasma

Threonine oxidation to glycine was investigated in vivo in twelve growing pigs (27·4 kg live weight) fed on one of the following three diets with graded levels of threonine supply: a low-threonine diet (LT), a control well-balanced diet (C) or a high-threonine diet (HT), during 10h constant infusion of L-[1-13C]threonine and [2-3H]glycine in the cranial vena cava and [l-14C]glycine in the portal vein.13C-threonine and glycine enrichments and [3H]glycine and [14C]glycine specific radioactivities (SR) were determined at plateau in peripheral venous plasma, liver and pancreas. Glycine praduction rates calculated from plasma [2-3H]glycine or [1-14C]glycine SR gave similar values suggesting that [l-14C]glycine SR could be used in order to estimate whole-body glycine flux. The high pancreas [1-13C]glycine enrichment provided evidence that the pancreas may be, with the liver, a major site of threonine oxidation to glycine. Moreover, the present findings suggest that threonine transport into the Liver could be the limiting step of threonine oxidation in this tissue when dietary threonine supply is low. Total threonine oxidation to glycine, calculated from plasma values of enrichment and specific radioactivity, was low and constant when the estimated absorbed threonine was lower than 4 g/d and increased for higher amounts of absorbed threonine.

A Three Degree of Freedom Lumped Parameter Model of Whole Body Vibration Along the Spine in the Rat

2013 ◽  
Author(s):  
Nicolas V. Jaumard ◽  
Hassam A. Baig ◽  
Benjamin B. Guarino ◽  
Beth A. Winkelstein
Keyword(s):  
Whole Body Vibration ◽  
Degree Of Freedom ◽  
Lumped Parameter Model ◽  
In Vivo Studies ◽  
Whole Body ◽  
Model Parameters ◽  
Body Vibration ◽  
Lumped Parameter ◽  
Three Degree Of Freedom

Whole body vibration (WBV) can induce a host of pathologies, including muscle fatigue and neck and low back pain [1,2]. A new model of WBV in the rat has been developed to define relationships between WBV exposures, kinematics, and behavioral sensitivity (i.e. pain) [3]. Although in vivo studies provide valuable associations between biomechanics and physiology, they are not able to fully define the mechanical loading of specific spinal regions and/or the tissues that may undergo injurious loading or deformation. Mathematical models of seated humans and primates have been used to estimate spinal loads and design measures that mitigate them during WBV [4–6]. Although such models provide estimates of relative spinal motions, they have limited utility for relating potentially pathological effects of vibration-induced kinematics and kinetics since those models do not enable simultaneous evaluation of relevant spinal tissues with the potential for injury and pain generation. As such, the goal of this work was to develop and validate a three degree of freedom (3DOF) lumped-parameter model of the prone rat undergoing WBV directed along the long-axis of the spine. The model was constructed with dimensions of a generalized rat and model parameters optimized using kinematics over a range of frequencies. It was validated by comparing predicted and measured transmissibility and further used to predict spinal extension and compression, as well as acceleration, during WBV for frequencies known to produce resonance in the seated human and pain in the rat [3,7].

scholarly journals A Kinetic Method for the Measurement of Zinc Influx In Vivo in the Rainbow Trout, and the Effects of Waterborne Calcium on Flux Rates

1989 ◽  
Vol 142 (1) ◽  
pp. 425-446 ◽  
Author(s):  
D. J. SPRY ◽  
C. M. WOOD
Keyword(s):  
Rainbow Trout ◽  
Plasma Sample ◽  
Kinetic Method ◽  
Whole Body ◽  
Constant Infusion ◽  
Linear Component ◽  
Experimental Apparatus ◽  
Body Counting ◽  
Whole Body Counting

Three methods were evaluated to measure rate of influx of Zn into rainbow trout. The first two, disappearance of 65Zn from the water and whole-body counting, overestimated influx when compared with a third method which used a terminal plasma sample to calculate influx. The cause of the overestimate was a short-term adsorption phenomenon to both the experimental apparatus and the exterior of the fish. The third method measured only Zn which entered the fish. This method entailed ‘calibration’ of cannulated trout by constant infusion of small amounts of radiolabelled Zn. This was analogous to the entry of Zn into fish across the gill. After 24–36 h of infusion, plasma radioactivity reached a steadystate concentration which was a simple linear function of the rate of infusion. This relationship was then used to predict influx from a single terminal plasma sample from uncannulated trout exposed to radiolabelled Zn in the water. Trout acclimated to tapwater (Ca2+ = 2.0 mequivl−1) and exposed to Zn (1.5-45.9 μequivl−1; 0.05-1.5 mgl−1) showed saturable uptake which was apparently first order with no significant linear component. The apparent Jmax and Km were 314 nequiv kg−1 h−1 and 7.3 μequivl−1 (0.24 mgl−1), respectively. Acutely raising the waterborne [Ca2+] (4.7 and 9.7 mequivl−1) over the same range of [Zn] revealed a competitive type of interaction - little change in Jmax, with increased Km. When Ca2+ was acutely removed (0.05 and 1.02 mequivl−1) by the use of artificial soft water, significant linear influx occurred in addition to the saturable uptake noted at higher [Ca2+], suggesting the opening of a paracellular leak. Calculation of the inhibitor constant for Ca2+ yielded a value of 0.48 mequivl−1. This value is similar to the Km for Ca2+ when it was a transported substrate (0.28 ± 0.07 mequivl−1). The true Km for Zn transport in the absence of Ca2+ was 1.0 μequivl−1 (0.06 mgl−1). These data showed Zn influx to be saturable and strongly dependent upon waterborne [Ca2+], perhaps traversing the gill in a manner similar to Ca2+.

Rapid determination of whole-body bicarbonate kinetics by use of a digital infusion

1984 ◽  
Vol 247 (4) ◽  
pp. R709-R716 ◽  
Author(s):  
C. S. Irving ◽  
W. W. Wong ◽  
W. M. Wong ◽  
T. W. Boutton ◽  
R. J. Shulman ◽  
...  
Keyword(s):  
Kinetic Parameters ◽  
Rapid Determination ◽  
Accurate Determination ◽  
Substrate Oxidation ◽  
Whole Body ◽  
Constant Infusion ◽  
External Control ◽  
Base Line ◽  
Oxidation Rates

Accurate determination of substrate oxidation rates from breath 13CO2 levels often requires information on the bicarbonate status of the subject. We have developed a rapid method to obtain a complete set of bicarbonate kinetic parameters, prime bicarbonate pools with 13C, clamp breath 13CO2 levels rapidly and accurately with predetermined ranges, and provide a steady base-line enrichment of 13C for a subsequent substrate oxidation measurement. The method consists of administering NaH13CO3 intravenously as a combination of a bolus dose, an exponentially decreasing infusion, and a constant infusion. A Harvard model 2729 microprocessor-controlled syringe pump was modified for external control and coupled to a Hewlett-Packard HP-85 desk-top computer to deliver the complex infusion. An infusion algorithm that would rapidly attain and maintain an increase of 50% 13C enrichment of breath CO2 was derived by using the SAAM-27 program to interrogate a three-compartmental model of bicarbonate kinetics in normal, fasted, resting adult subjects. When the method was tested on five adult fasted subjects who had rested for 1.5 h, plateau enrichments were achieved within 10–20 min. The bicarbonate pool sizes and kinetic parameters obtained by compartmental analysis of their 13CO2 data were used to obtain a refined infusion protocol, which resulted in more rapid attainment of plateau enrichments. If carried out immediately before a substrate oxidation test, the method can provide a complete description of bicarbonate kinetics for use in the compartmental and noncompartmental analysis of substrate catabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

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