Recycling of an amino acid label with prolonged isotope infusion: implications for kinetic studies

1985 ◽  
Vol 248 (4) ◽  
pp. E482-E487 ◽  
Author(s):  
W. F. Schwenk ◽  
E. Tsalikian ◽  
B. Beaufrere ◽  
M. W. Haymond

To investigate whether recycling of a labeled amino acid would occur after 24 h of infusion, two groups of normal volunteers were infused with [3H]leucine and alpha-[14C]-ketoisocaproate for 4 h and [2H3]leucine for either 4 or 24 h (groups I and II, respectively). Entry of [2H3 )leucine at steady state into the plasma space was indistinguishable from its infusion rate for group I but 30% higher (P less than 0.001) than this rate for group II, demonstrating significant recycling of label. After discontinuation of the infusions, isotope disappearance from the plasma space was followed for 2 h. The 3H and 14C decay data for both groups suggest that plasma leucine and alpha-ketoisocaproate are derived from a single intracellular pool in the postabsorptive state. In group I, the 3H and 2H labels decayed identically; whereas, in group II, the decay of [2H3]-leucine and alpha-[2H3]ketoisocaproate was slower (P less than 0.01) than the decay of [3H]leucine and alpha-[3H]ketoisocaproate, confirming re-entry of label after a 24-h infusion. Therefore kinetic values calculated from models assuming no recycling of labeled amino acids are most likely not quantitative and must be interpreted with care when flux does not change or decreases.

Author(s):  
M. Saravanakumar ◽  
A.V. Elangovan ◽  
V.B. Awachat ◽  
A.K. Pattanaik ◽  
A. Dhali ◽  
...  

Background: In ovo supplementation of nutrients either amino acids or minerals in broiler chicken has been common more often individually or few nutrients with positive results. In view of the above, in ovo supplementation with combination of amino acids and minerals as a complete nutrient capsule for the gut and immune system development was tested for hatchability since the modern commercial broilers are very fragile to any changes in the internal environment. Methods: Four trials were conducted to study the response of in ovo supplementation of combinations of Lys, Met, Arg, Thr, Glu, Zn, Se and Cu on hatchability of broiler eggs. In trial I, the fertile eggs on day 18 were divided into five groups of 32 eggs in each group. Group I served as control without any amino acids and mineral supplementation. Group II, III, IV and V supplemented with Lys, Met, Arg, Thr, Glu, Zn, Se and Cu @ 2.2, 1, 2.5, 1.6, 2.5 mg, 80, 0.3, 16 µg; 4.4, 2, 5, 3.2, 5 mg, 80, 0.3, 16 µg; 11, 5, 12.5, 8, 12.5 mg, 80, 0.3, 16 µg and 22, 10, 25, 16, 25 mg, 80, 0.3, 18 µg respectively. In trial II, seventy fertile eggs were divided into seven groups, Group I served as control. Group II, III, IV, V, VI and VII were supplemented with graded levels (1x to 6x) of amino acids. The 1x consisted of Lys, Met, Arg, Thr and Glu @ 2.2, 1, 2.5, 1.6 and 2.5 mg, respectively. On day 18, 10 eggs per group were supplemented with graded levels of AA combination into the amniotic fluid. In trail III and IV it was similar to trial II but was without Lys and Met, respectively. Result: Results indicated that hatchability (Trial 1) in Group V, IV, III, II and I were 0, 18, 21.8, 71 and 90.6%, respectively. The Combination of five amino acids (Trial II) (Lys, Met, Thr, Arg, Glu) for in ovo supplementation reduced the hatchability, whereas, combination of four amino acids (Trial III) (Met, Thr, Arg, Glu) without Lys at lower doses resulted in good hatchability (86.6%). In ovo supplementation of amino acid or mineral-amino acid combinations in commercial broiler eggs should be restricted to few amino acids.


1988 ◽  
Vol 254 (5) ◽  
pp. E588-E594 ◽  
Author(s):  
H. Lochs ◽  
P. E. Williams ◽  
E. L. Morse ◽  
N. N. Abumrad ◽  
S. A. Adibi

Oligopeptides may enter the bloodstream from endogenous and exogenous sources. Using an organ-balance technique in conscious dogs, we investigated the role of individual organs in removal of two model oligopeptides (glycylleucine and glycylglycine) from plasma under steady-state conditions. Despite an identical infusion rate, arterial concentration of glycylglycine was twofold greater than that of glycylleucine. This appeared to be a result of greater fractional extraction of glycylleucine than glycylglycine by organs. Although all of the organs examined participated in removal of dipeptides from plasma, their roles varied. Liver, kidney, muscle, and gut accounted for the disappearance of 25, 24, 12, and 10% of the infused amount of glycylleucine, respectively. With glycylglycine as the substrate, disappearance across kidney accounted for 37% of the infused amount, whereas muscle, liver, and gut accounted for 18, 15, and 11%, respectively. Finally, we investigated glycine and leucine balances across organs with infusion of these amino acids in free and dipeptide forms. Glycine and leucine balances were uniquely more positive across muscle during the infusion of glycylleucine than the corresponding amino acid mixture. The possible mechanisms included release of products of glycylleucine hydrolysis by all organs except muscle. We conclude that molecular structure influences the organ extraction of dipeptides; if extraction, particularly by the liver, is not sufficiently rapid, kidney assumes a greater role than other organs in dipeptide removal from plasma.


1992 ◽  
Vol 262 (6) ◽  
pp. E925-E935 ◽  
Author(s):  
M. Frexes-Steed ◽  
D. B. Lacy ◽  
J. Collins ◽  
N. N. Abumrad

The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L-leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation.


1994 ◽  
Vol 267 (6) ◽  
pp. E877-E885 ◽  
Author(s):  
I. Tauveron ◽  
D. Larbaud ◽  
C. Champredon ◽  
E. Debras ◽  
S. Tesseraud ◽  
...  

The experiment was carried out to clarify the roles of insulin and amino acids on protein synthesis in fed lactating goats (30 days postpartum). Protein synthesis in the liver and various skeletal muscles was assessed after an intravenous injection of a large dose of unlabeled valine containing a tracer dose of L-[2,3,4-3H]valine. The animals were divided into three groups. Group I was infused with insulin (1.7 mumol/min) for 2.5 h under glucose, potassium, and amino acid replacement. Group A was infused with an amino acid mixture to create stable hyperaminoacidemia for 2.5 h. Group C animals were controls. The fractional synthesis rates (FSR) were 31.5 +/- 2.2, 6.5 +/- 0.4, 4.3 +/- 0.8, 4.0 +/- 1.2, 3.9 +/- 1.2, and 3.6 +/- 0.4%/day (SD) in liver, masseter, diaphragm, anconeus, semitendinosus, and longissimus dorsi, respectively, for group C. Neither hyperinsulinemia in group I nor hyperaminoacidemia in group A had not affected by hyperinsulinemia but was stimulated by hyperaminoacidemia (+30%, P < 0.05). In contrast to previous experiments in which a labeled amino acid was constantly infused, this study revealed a stimulating effect of amino acids on protein synthesis in the liver but not in skeletal muscles. As previously observed in studies with the constant-infusion method, insulin had no effect on protein synthesis.


1991 ◽  
Vol 260 (1) ◽  
pp. E111-E117 ◽  
Author(s):  
R. A. Hoerr ◽  
D. E. Matthews ◽  
D. M. Bier ◽  
V. R. Young

In amino acid tracer kinetic studies of the fed state, ingested amino acid may be taken up during its initial transit through splanchnic tissues and thus not enter the plasma compartment where tracer is infused. To investigate this possibility, adult human subjects received simultaneous intravenous (iv) and intragastric (ig) leucine tracer infusions, first during a postabsorptive (PA) 4-h primed continuous ig infusion of L-[1-13C]-leucine and L-[5,5,5-2H3]leucine iv, followed on a separate day by a fed infusion, in which an ig infusion of a liquid formula was started 2 h before the tracer infusion and continued throughout the tracer study. Subjects were accustomed to a constant experimental diet supplying 1.5 g protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and fed studies, respectively. For the PA study, plasma enrichment for the ig tracer was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/- 0.16 (ig) and 3.02 +/- 0.14 (iv), respectively [not significant (NS)]. For the fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/- 0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and in the fed experiment, 0.76 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 267 (5) ◽  
pp. F703-F708 ◽  
Author(s):  
M. Giordano ◽  
P. Castellino ◽  
E. L. McConnell ◽  
R. A. DeFronzo

We evaluated the dose-response relationship between the plasma amino acid (AA) concentration and renal hemodynamics in eight normal subjects. After an overnight fast, a balanced 10% AA solution was infused for 180 min at five separate infusion rates: 0.5 (group I), 1.0 (group II), 2.0 (group III), 4.0 (group IV), and 6.0 (group V) ml.kg-1.min-1 on separate days. Basal plasma AA concentration was 1.87 +/- 0.1 mmol/l and increased to 2.26 +/- 0.1 (group I), 2.66 +/- 0.2 (group II), 3.79 +/- 0.5 (group III), 5.81 +/- 0.4 (group IV), and 7.41 +/- 0.4 mmol/l (group V). Basal glomerular filtration rate (GFR) and renal plasma flow (RPF) averaged 95 +/- 4 and 476 +/- 29 ml.1.73 m-2.min-1, respectively, and rose to 98 +/- 5 and 506 +/- 40 (group I) [P = not significant (NS)], 102 +/- 3 and 533 +/- 30 (group II) (P < 0.05 vs. basal), 110 +/- 4 and 567 +/- 29 (group III), 115 +/- 7 and 610 +/- 55 (group IV), and 117 +/- 7 and 614 +/- 66 ml.1.73 m-2.min-1 (group V) (P = NS vs. group IV). Basal plasma glucagon concentration averaged 68 +/- 10 pg/ml and increased to 74 +/- 10 (group I), 83 +/- 11 (group II) (P < 0.05 vs. basal), 100 +/- 14 (group III), 121 +/- 14 (group IV), and 229 +/- 35 pg/ml (group V) (P < 0.01 vs. basal). Increases in plasma growth hormone (GH) and insulin levels were observed only during groups IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)


2013 ◽  
Vol 5 (2) ◽  
pp. 101 ◽  
Author(s):  
Ritawaty Ritawaty ◽  
Indriyanti Rafi Sukmawati ◽  
Ilhamjaya Patellongi ◽  
Ferry Sandra

BACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed.METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC >100 cm, without fatty liver; Group IV: WC >100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed.RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV.CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC >100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.KEYWORDS: GGT, hs-CRP, GPx, tCys, HOMA-IR, insulin resistance


1982 ◽  
Vol 242 (1) ◽  
pp. E53-E58
Author(s):  
J. G. Yovos ◽  
T. M. O'Dorisio ◽  
T. N. Pappas ◽  
S. Cataland ◽  
F. B. Thomas ◽  
...  

Insulin release following intravenous administration of an amino acid solution with and without a simultaneous infusion of varying amounts of porcine gastric inhibitory polypeptide (GIP) was studied in dogs. Group I received a 10-amino acid mixture (300 mosmol/kg iv) at 16.6 ml/min for 1 h; group II, amino acid mixture plus 0.5 micrograms.kg-1.h-1 porcine GIP; group III, amino acid mixture plus 1.0 micrograms.kg-1.h-1 of GIP; group IV (a and b) received either 0.5 or 1.0 micrograms.kg-1.h-1 of GIP alone. Compared to group I, groups II and III had a greater insulin response during the first 30 min of the infusion. Group] IV (a and b) showed no insulin release. Glucose concentrations showed no significant change in all groups. From these results, it is concluded that insulin release after intravenous infusion of an amino acid mixture plus GIP is greater than after amino acids or GIP alone. It appears that this effect is more pronounced in the early phase of insulin release.


2013 ◽  
Vol 24 (1) ◽  
pp. 12-15
Author(s):  
Kamrun Nahar ◽  
Zeba-un Naher ◽  
Matira Khanam ◽  
Shaheen Akhter ◽  
Tahmina Bashar ◽  
...  

Adequate nutritional support may prevent weight loss  following severe burn injury. However, persistently low  levels of serum albumin, transferring and serum total  protein in burn patients have suggested that a protein  deficiency may continue to exist which is out of proportion  to energy requirements.  This interventional study cross sectional study was done in  the Department of Biochemistry, Bangabandhu Sheikh  Mujib Medical University (BSMMU), Dhaka, Bangladesh  during January 2008 to December 2008. A total of 40 acute  burn injury (within 24 hours of burn) patients of 20-45  years age with 15%-30% burn were selected for this study  as case. The study subjects were divided into two groups:  Group I represent superficial burn & Group II represents  deep burn.  The mean age of 28.35±6.81 years and 30.85±7.32 years in  group I and group II respectively. The number of male in  Group-I was 08 and Group-II was 08 and male female ratio  was 2:3. The mean serum total protein before infusion of  amino acid in Group-I was 55.31±3.58 g/L and in Group-II  was 52.01±2.26 g/L (p<0.001). The mean serum total  protein after infusion of amino acid in Group-I was  68.02±2.04 g/L and in Group-II was 61.86±2.49g/L  (p<0.001). The mean serum albumin before infusion of  amino acid in Group-I was 27.6±2.88 g/L and in Group-II  was 25.57±1.89 g/L (p<0.001). The mean serum albumin  after infusion of amino acid in Group-I was 22.29±3.50 g/L  and in Group-II was 19.83±2.86 g/L (p<0.001). In group-I,  serum total protein was increased by 22.98% after infusion  and in group-II, that was increased by 18.94% (p<0.01).  In group-I, serum albumin was decreased by 19.24% after  infusion and in group-II, that was decreased by 22.45%  (p<0.05). Serum total protein significantly increased after  infusion of amino acid but serum albumin significantly  decreased after infusion of amino acid. DOI: http://dx.doi.org/10.3329/medtoday.v24i1.14107 Medicine TODAY Vol.24(1) 2012 pp.12-15


1996 ◽  
Vol 40 (3) ◽  
pp. 609-612 ◽  
Author(s):  
A Ayestarán ◽  
R M López ◽  
J B Montoro ◽  
A Estíbalez ◽  
L Pou ◽  
...  

The pharmacokinetics of amphotericin B administered in a conventional 5% dextrose (glucose) (5% D) solution and in a 20% fat emulsion formulation (Intralipid; 20% IL) were compared in 16 patients (mean age, 42 years [range, 18 to 70 years]) who had been hospitalized for hematological malignancies and with proven or suspected fungal infections. All of the patients received 50 mg (approximately 1 mg/kg of body weight per day) of amphotericin B daily in random order, either as a 50-ml lipid emulsion (20% IL) (group I) or in 500 ml of 5% D (group II). Five serum samples were taken during the 24 h after drug administration, and the levels of amphotericin B were measured by high-pressure liquid chromatography. Serum amphotericin B concentrations declined rapidly during the first 6 h, and subsequent measurements revealed a slow terminal elimination phase in both groups. The maximum serum amphotericin B concentration was significantly lower when the drug was administered in 20% IL (1.46 +/- 0.61 versus 2.83 +/- 1.17 micrograms/ml; P = 0.02). The area under the concentration-time curve from 0 to 24 h was also much lower in group I (17.22 +/- 11.15 versus 28.98 +/- 15.46 micrograms.h/ml). The half-life of the distribution phase was approximately three times longer in group I (2.92 +/- 2.34 h versus 0.64 +/- 0.24 h; P = 0.011). Conversely, the half-lives of the elimination phase were approximately equal in the two groups (11.44 +/- 5.18 versus 15.23 +/- 5.25 h). The mean residence times were also similar in both groups (19.41 +/- 11.13 versus 19.65 +/- 7.86 h). The clearance and the steady-state volume of distribution of amphotericin B in group I were about twice as great as those in group II (62.97 +/- 35.51 versus 33.01 +/- 14.33 ml/kg/h and 1,043.92 +/- 512.10 versus 562.32 +/- 152.05 ml/kg [P = 0.034], respectively). Finally, the volume of distribution in the central compartment was greater in group I than in group II (618.17 +/- 231.80 versus 328.19 +/- 151.71 ml/kg; P = 0.013), but there were no differences in the volume of distribution in the peripheral compartment (425.75 +/- 352.87 versus 234.14 +/- 75.92 ml/kg). These results suggest that amphotericin B has a different pharmacokinetic profile when it is administered in 20% IL than when it is administered in the standard 5% D form and that the main difference is due to a clear-cut difference in the steady-state volume of distribution, especially that in the central compartment.


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