Arginine, citrulline and nitric oxide metabolism in sepsis

2009 ◽  
Vol 117 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Christina C. Kao ◽  
Venkata Bandi ◽  
Kalpalatha K. Guntupalli ◽  
Manhong Wu ◽  
Leticia Castillo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Asymmetric Dimethylarginine ◽  
De Novo ◽  
Plasma Concentrations ◽  
No Synthase ◽  
Whole Body ◽  
Healthy Controls ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Body Protein

Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and immunomodulatory actions which play important roles in sepsis. Protein breakdown affects arginine availability and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore affect NO synthesis in patients with sepsis. The objective of the present study was to investigate whole-body in vivo arginine and citrulline metabolism and NO synthesis rates, and their relationship to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically ill patients with sepsis or septic shock and seven healthy controls using an intravenous infusion of [1-13C]leucine. Arginine flux, citrulline flux and the rate of conversion of arginine into citrulline (an index of NO synthesis) were measured with intravenous infusions of [15N2]guanidino-arginine and [5,5-2H2]citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were measured. Compared with controls, patients had a higher leucine flux and higher NO metabolites, but arginine flux, plasma asymmetric dimethylarginine concentration and the rate of NO synthesis were not different. Citrulline flux and plasma arginine and citrulline were lower in patients than in controls. Arginine production was positively correlated with the protein breakdown rate. Whole-body arginine production and NO synthesis were similar in patients with sepsis and septic shock and healthy controls. Despite increased proteolysis in sepsis, there is a decreased arginine plasma concentration, suggesting inadequate de novo synthesis secondary to decreased citrulline production.

The Independent Effect of Propofol Anesthesia on Whole Body Protein Metabolism in Humans

1999 ◽  
Vol 90 (6) ◽  
pp. 1636-1642. ◽  
Author(s):  
Thomas Schricker ◽  
Kristine Klubien ◽  
Franco Carli
Keyword(s):  
Fatty Acids ◽  
Protein Synthesis ◽  
General Anesthesia ◽  
Protein Metabolism ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Independent Effect ◽  
Protein Breakdown ◽  
Body Protein ◽  
Esterified Fatty Acids

Background The purpose of this study was to examine the effect of general anesthesia with propofol in the absence of surgical stimulation on whole body protein metabolism. Methods Six unpremedicated patients were studied. General anesthesia included propofol (120 microg x kg(-1) x min(-1)), vecuronium bromide, and oxygen-enriched air. Changes in protein breakdown, protein oxidation, and synthesis were measured by an isotope dilution technique using a constant infusion of the stable isotope tracer L-[1-13C]leucine (0.008 mg x kg(-1) x min(-1)) before and during 100 min of propofol anesthesia. The plasma concentrations of glucose, lactate, non-esterified fatty acids, and cortisol were measured before and during anesthesia. Results An isotopic steady state of plasma [1-13C]alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) and expired 13C-carbon dioxide were obtained before and during propofol infusion. Whole body protein breakdown decreased during propofol anesthesia by 6% (P < 0.05), whereas protein synthesis and oxidation did not change significantly. Plasma concentration of cortisol decreased after 90 min of propofol anesthesia (P < 0.05). No significant changes of plasma concentrations of glucose, lactate, and non-esterified fatty acids occurred during propofol administration. Conclusions Propofol anesthesia did not significantly affect whole body protein synthesis and oxidation but caused a small, although significant, decrease in whole body protein breakdown, possibly mediated through the suppression of plasma cortisol concentration.

The acute-phase protein response to human immunodeficiency virus infection in human subjects

1999 ◽  
Vol 276 (6) ◽  
pp. E1092-E1098 ◽  
Author(s):  
Farook Jahoor ◽  
Brian Gazzard ◽  
Gary Phillips ◽  
Danny Sharpstone ◽  
Melanie Delrosario ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Human Immunodeficiency Virus Infection ◽  
Acute Phase ◽  
Protein Turnover ◽  
Plasma Concentrations ◽  
Retinol Binding Protein ◽  
Whole Body ◽  
Body Protein ◽  
Immunodeficiency Virus

Although several studies have shown that asymptomatic human immunodeficiency virus infection elicits an increase in whole body protein turnover, it is not known whether this increased protein turnover includes changes in the kinetics of acute-phase proteins (APPs). To answer this question, we measured 1) the plasma concentrations of four positive (C-reactive protein, α1-antitrypsin, haptoglobin, and fibrinogen) and four negative APPs [albumin, high-density lipoprotein (HDL)-apolipoprotein (apo) A1, transthyretin, and retinol-binding protein] and 2) the fractional (FSR) and absolute (ASRs) synthesis rates of three positive and three negative APPs using a constant intravenous infusion of [2H5]phenylalanine in five subjects with symptom-free acquired immunodeficiency syndrome (AIDS) and five noninfected control subjects. Compared with the values of the controls, the plasma concentrations, FSRs, and ASRs of most positive APPs were higher in the AIDS group. The negative APPs had faster FSRs in the AIDS group, there was no difference between the ASRs of the two groups, and only HDL-apoA1 had a lower plasma concentration. These results suggest that symptom-free AIDS elicits an APP response that is different from bacterial infections, as the higher concentrations and faster rates of synthesis of the positive APPs are not accompanied by lower concentrations and slower rates of synthesis of most of the negative APPs.

scholarly journals The impact of Hayward green kiwifruit on dietary protein digestion and protein metabolism

2020 ◽  
Author(s):  
Sanghee Park ◽  
David D. Church ◽  
Carlene Starck ◽  
Scott E. Schutzler ◽  
Gohar Azhar ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Protein Digestion ◽  
Body Protein ◽  
Before And After ◽  
The Impact ◽  
Green Kiwifruit

Abstract Purpose The purpose of the study was to determine if an actinidin protease aids gastric digestion and the protein anabolic response to dietary protein. Methods Hayward green kiwifruit (containing an actinidin protease) and Hort 16A gold kiwifruit (devoid of actinidin protease) were given in conjunction with a beef meal to healthy older subjects. Twelve healthy older males (N = 6) and females (N = 6) were studied with a randomized, double-blinded, crossover design to assess muscle and whole-body protein metabolism before and after ingestion of kiwifruit and 100 g of ground beef. Subjects consumed 2 of each variety of kiwifruit daily for 14 d prior to each metabolic study, and again during each study with beef intake. Results Hayward green kiwifruit consumption with beef resulted in a more rapid increase in peripheral plasma essential amino acid concentrations. There were significant time by kiwifruit intake interactions for plasma concentrations of EAAs, branched chain amino acids (BCAAs), and leucine (P < 0.01). However, there was no difference in the total amount of EAAs absorbed. As a result, there were no differences between kiwifruit in any of the measured parameters of protein kinetics. Conclusion Consumption of Hayward green kiwifruit, with a beef meal facilitates protein digestion and absorption of the constituent amino acids as compared to Hort 16A gold kiwifruit. Clinical trial NCT04356573, April 21, 2020 “retrospectively registered”.

scholarly journals Alterations in glutamine metabolism and its conversion to citrulline in sepsis

2013 ◽  
Vol 304 (12) ◽  
pp. E1359-E1364 ◽  
Author(s):  
Christina Kao ◽  
Jean Hsu ◽  
Venkata Bandi ◽  
Farook Jahoor
Keyword(s):  
Severe Sepsis ◽  
Plasma Concentration ◽  
Metabolic Pathways ◽  
Plasma Concentrations ◽  
Glutamine Metabolism ◽  
Whole Body ◽  
Healthy Controls ◽  
Metabolic Fate ◽  
Sequential Administration ◽  
Gut Function

In enterocytes, glutamine serves as the major source of energy; another metabolic fate of glutamine is conversion to citrulline. Because sepsis can affect gut function and integrity, alterations in glutamine metabolism may exist and lead to decreased citrulline production. This study aimed to investigate how sepsis affects glutamine metabolism, including its conversion to citrulline, by measuring glutamine and citrulline flux, fractional splanchnic extraction of glutamine and leucine, and the contribution of glutamine nitrogen to citrulline in septic patients and healthy controls. Eight patients with severe sepsis and 10 healthy controls were given primed, constant intravenous infusion of [2H2]citrulline and sequential administration of intravenous and enteral [α-15N]glutamine and [13C]leucine in the postabsorptive state. The results showed that, compared with healthy controls, septic patients had a significantly lower whole body citrulline flux and plasma concentration, higher endogenous leucine flux, and higher glutamine clearance. Fractional splanchnic extraction of leucine was higher in septic patients than in controls, but fractional extraction of glutamine was not different. The majority of the 15N label transferred from glutamine to citrulline was found at the α-position. These results demonstrate that lower glutamine plasma concentrations in sepsis were a result of increased glutamine clearance. Despite adequate splanchnic uptake of glutamine, there is decreased production of citrulline, suggesting a defect in the metabolic conversion of glutamine to citrulline, decreased uptake of glutamine by the enterocyte but increased uptake by the liver, and/or shunting of glutamine to other metabolic pathways.

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth

1991 ◽  
Vol 261 (1) ◽  
pp. R106-R116
Author(s):  
N. W. Istfan ◽  
P. R. Ling ◽  
G. L. Blackburn ◽  
B. R. Bistrian
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Whole Body ◽  
Independent Effect ◽  
Yoshida Sarcoma ◽  
Protein Breakdown ◽  
Body Protein ◽  
Breakdown Rates ◽  
Made In

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of “whole body” protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism

1998 ◽  
Vol 274 (5) ◽  
pp. E801-E807 ◽  
Author(s):  
Dominique Darmaun ◽  
Susan Welch ◽  
Annie Rini ◽  
Brenda K. Sager ◽  
Astride Altomare ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Oral Treatment ◽  
Healthy Adults ◽  
Whole Body ◽  
Dependent Manner ◽  
Glutamine Concentration ◽  
Body Protein ◽  
Healthy Humans ◽  
Appearance Rate

The present study was designed to determine whether sodium phenylbutyrate (ΦB) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g ⋅ kg−1 ⋅ day−1) of ΦB were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an ≈25% decline for a dose of 0.36 g ΦB ⋅ kg−1 ⋅ day−1. A second group of six healthy adults received 5-h infusions ofl-[1-14C]leucine andl-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with ΦB (0.36 g ⋅ kg−1 ⋅ day−1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an ≈26% decline in plasma glutamine concentration from 514 ± 24 to 380 ± 15 μM (means ± SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 ± 7 vs. 117 ± 5 μmol ⋅ kg−1 ⋅ h−1; not significant); 3) an ≈22% rise in leucine oxidation (Ox) from 23 ± 2 to 28 ± 2 μmol ⋅ kg−1 ⋅ h−1( P < 0.01), resulting in an ≈11% decline in nonoxidative leucine disposal (NOLD = Ra − Ox), an index of protein synthesis, from 100 ± 6 to 89 ± 5 μmol ⋅ kg−1 ⋅ h−1( P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a “glutamine trap” to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decreases estimates of whole body protein synthesis.

Plasma insulin concentrations and amino acid turnover in Merino sheep with high or low fleece weight

2004 ◽  
Vol 55 (8) ◽  
pp. 833 ◽  
Author(s):  
N. R. Adams ◽  
S. M. Liu ◽  
J. R. Briegel ◽  
M. J. Thompson
Keyword(s):  
Amino Acids ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Amino Nitrogen ◽  
Whole Body ◽  
Metabolic Demand ◽  
Body Protein ◽  
Wool Growth ◽  
Staple Strength ◽  
Fleece Weight

Although sheep with a relatively high fleece weight have reduced fat deposition and a lower reproductive rate, research has failed to identify any specific metabolic demand that growing a fleece places on the physiology of the sheep. This paper reports two experiments in which the effect of fleece weight was examined in ewes infused intravenously with amino acids. The first experiment was carried out when the ewes were 107 days pregnant, and the second 2 years later in non-pregnant ewes from the same flock. The ewes were derived initially from groups that differed in staple strength, but there was no effect of staple strength group on the characteristics measured in either experiment. In Expt 2, ewes were also infused with a bolus of l-[ring-d5] phenylalanine, and the enrichment in plasma determined by GC/mass spectrometry over the next 24 h. In both experiments, fasting plasma insulin concentrations were lower (P < 0.05) in ewes with a high fleece weight, and this difference continued during infusion in Expt 2 (P < 0.05). In Expt 1, infusion of ewes with amino acids resulted in higher (P < 0.05) plasma concentrations of α-amino nitrogen (indicating amino acids) in the ewes with a higher fleece weight, and in Expt 2, ewes with a high fleece weight had a 19% higher rate of appearance of endogenous phenylalanine (P < 0.05). We conclude that sheep with high wool growth rates have higher whole-body protein turnover rate, which may be achieved in part by lower insulin concentrations. Lower insulin in turn provides a mechanism through which wool growth rate may influence energy availability to other tissues.

Whole-Body Protein Turnover before and after Resection of Colorectal Tumours

1983 ◽  
Vol 64 (1) ◽  
pp. 101-108 ◽  
Author(s):  
R. E. Glass ◽  
E. B. Fern ◽  
P. J. Garlick
Keyword(s):  
Protein Synthesis ◽  
Primary Tumour ◽  
Experimental Period ◽  
Whole Body ◽  
Tumour Resection ◽  
Surgical Removal ◽  
Protein Breakdown ◽  
Nitrogen Flux ◽  
Body Protein ◽  
Before And After

1. The rate of whole-body nitrogen flux; protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A—C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.

scholarly journals A four-compartment compartmental model to assess net whole body protein breakdown using a pulse of phenylalanine and tyrosine stable isotopes in humans

2017 ◽  
Vol 313 (1) ◽  
pp. E63-E74 ◽  
Author(s):  
Alvise Mason ◽  
Mariëlle P. K. J. Engelen ◽  
Ivan Ivanov ◽  
Gianna M. Toffolo ◽  
Nicolaas E. P. Deutz
Keyword(s):  
Stable Isotopes ◽  
A Priori ◽  
Flux Ratio ◽  
Fat Free Mass ◽  
Whole Body ◽  
Protein Breakdown ◽  
Detailed Model ◽  
Body Protein ◽  
Health And Disease ◽  
Net Protein

The stable isotopes of phenylalanine (Phe) and tyrosine (Tyr) are often used to study whole body protein metabolism in humans. Noncompartmental approaches give limited physiological insight in the compartmental characteristics. We therefore developed a compartmental mathematical model of Phe/Tyr metabolism to describe protein fluxes by using stable tracer dynamic data in plasma following intravenous bolus of l-[ring-13C6]Phe and l-[ ring-2H4]Tyr in healthy subjects. The model consists of four compartments describing Phe/Tyr kinetics. Because the model is a priori nonidentifiable, it is quantified in terms of two uniquely identifiable submodels representing two limit case scenarios, based on known physiology. The two submodels, identified by using the software SAAM II, fit well the experimental data of all individuals and provide an unbiased overview of the metabolic pathway in terms of intervals of validity of the non-uniquely identifiable variables. The model provides estimates of the flux from Phe to Tyr [4.1 ± 1.0 µmol·kg fat-free mass (FFM)−1·h−1 (mean ± SE)] and intervals of validity of the flux and pool estimates. Our preferred submodel yielded protein breakdown flux (50.5 ± 5.2 µmol·kg FFM−1·h−1), net protein breakdown (4.1 ± 1.0 µmol·kg FFM−1·h−1), Tyr from Phe hydroxylation (~12%), hydroxylated Phe (~8%), and flux ratio of Tyr to Phe arising from protein catabolism (0.68), consistent with available literature. The other submodel suggest that the assumptions made by noncompartmental analysis are consistently underestimated. Our accurate and detailed model for estimating Phe/Tyr metabolic pathways in humans might be essential to applications in a variety of scenarios describing whole body protein synthesis and breakdown in health and disease.

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