![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
*
Department of Surgery, University Hospital Maastricht, NL-6202 AZ Maastricht, The Netherlands; and
Department of Human Biology, Maastricht University, NL-6200 MD Maastricht, The Netherlands
2To whom correspondence should be addressed.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KEY WORDS: • glutamine metabolism • trauma • humans • stable isotopes • protein degradation
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
, Deutz et al. 1992
, Douglas and Shaw 1989
, Wannemacher 1977
). It has been postulated that these processes serve the
purpose of supplying fuel for energy generation and building blocks for
the synthesis of specific proteins involved in the immunological
response and in the restoration of damaged tissue.
Glutamine has a pivotal role as major gluconeogenic precursor and
vehicle for interorgan carbon and nitrogen transport (Nurjhan et al. 1995
). Among the many other functions of glutamine are its
role as metabolic substrate for cells with a high turnover rate such as
immune cells, enterocytes and renal tubular cells (Ardawi and Newsholme 1983
, Windmueller 1982
), its function
as a precursor for purines, pyrimidines and glutathione (Cao et al. 1998
, Lacey and Wilmore 1990
), and its
central role in the regulation of acid-base homeostasis
(Halperin et al. 1990
). In pigs, we observed an
increased muscle glutamine production and a simultaneous rise in
glutamine consumption by liver and spleen 1–2 d after surgery
(Deutz et al. 1992
). Likewise, in human studies
arteriovenous difference measurements across arm or leg have shown a
two-fold increase in the net release of glutamine during sepsis or
trauma (Carli et al. 1990
, Clowes et al. 1980
, Mjaaland et al. 1993
,
Stjernström et al. 1986
), indicating a significant
rise in muscle glutamine production. Data in humans regarding the
effect of sepsis or trauma on glutamine production from organs and
tissues other than muscle are lacking, due to the invasive character of
such measurements. We hypothesized that during the metabolic stress of
major elective surgery the appearance rate
(Ra)3
of glutamine at the whole body level is
enhanced to meet the increased requirements of the organism for
glutamine.
Patients undergoing elective abdominal surgery were measured before operation and on the second postoperative day. Glutamine Ra was determined with the traditional tracer dilution method, using a primed continuous infusion of stable isotope labeled glutamine. Tracer methodology was also used to assess whole body protein turnover in order to relate changes in glutamine Ra to surgery-induced alterations in whole body protein breakdown.
|
PATIENTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Fourteen patients (aged 58–78 y, 8 men and 6 women) admitted to the hospital for elective abdominal surgery participated in the study. Underlying diseases were colorectal cancer (n = 6), gastric cancer (n = 1), pancreatic cancer (n = 1), villous adenoma (n = 2), diverticular disease (n = 3) and Crohn’s disease (n = 1). No clinical signs of inflammatory activity were present. Body weight averaged 73 ± 4 kg and was stable in all subjects, except in three patients who had suffered a recent weight loss of ~10% over the last 6 mo. Body mass index was 25.9 ± 1.1 kg/m2. Written informed consent was obtained from all patients, and the protocol was approved by the Medical Ethics Committee of the University Hospital Maastricht.
Study design.
The measurements were performed 1 or 2 d before surgery and on the second postoperative day. Preoperatively, the patients were fasted overnight and remained fasted until the study was completed. In the period between surgery and the postoperative measurement, fluid balance was maintained with normal saline and glucose 50 g/L (2–3 L/d, 850–1250 kJ per 24 h) according to standard protocol. Patients had a zero nitrogen intake during this period.
The patients were operated in epidural analgesia with local anesthetics and opiates (bupivacaine and sufentanyl) in addition to general anesthesia. The epidural catheter was left in place during 1–4 d after surgery. In 9 patients the epidural infusion of local anesthetics and opiates was continued during the postoperative measurements. In the other subjects the measurements were carried out after the epidural block had been withdrawn.
In the morning of each study, patients received a catheter in an
antecubital vein for isotope infusion and another in the radial artery
for blood sampling. The arterial catheter was kept patent by a slow
saline infusion. Glucose infusion was stopped during the experiments.
At 0830 h a primed constant intravenous infusion of
L-[5-15 N]glutamine (0.68 µmol
· kg-1 · h-1; prime 0.68
µmol/kg) and L-[1-13C]leucine (7.63 µmol
· kg-1 · h-1; prime 7.63 µmol/kg) was
given for 6 h. The tracers were purchased from Cambridge Isotope
Laboratories (Woburn, MA). Blood samples were drawn in chilled-on-ice
heparinized tubes before the start of the tracer infusion for
measurement of baseline enrichment and at 2, 3, 4, 5 and 6 h after
onset of the infusion. Plasma was obtained by centrifugation of whole
blood at 2,200 x g at 4°C for 5 min. For the
determination of plasma glutamine concentration, plasma was
deproteinized with sulfosalicylic acid (van Eijk et al. 1994
), mixed
with a vortex mixer, frozen in liquid nitrogen and stored at -80°C.
For tracer enrichment measurements, plasma was frozen and stored at
-80°C until analysis. In 8 patients, percutaneous muscle biopsies
were taken from the anterior tibial muscle once or twice during each
tracer infusion to measure glutamine enrichment and concentration in
the intracellular free glutamine pool in muscle. Biopsies were taken
using the conchotome technique (Dietrichson et al. 1987
). Blood, visible fat and connective tissue were quickly
removed from the specimen, and the tissue was immediately frozen in
liquid nitrogen and subsequently stored at -80°C for later analysis.
To limit the number of biopsies in each patient, baseline enrichment in
muscle was assumed to be equal to the enrichment in plasma. Support for
this assumption comes from a previous study in a similar group of
preoperative patients. By extrapolating back to time zero the glutamine
enrichment data in successive muscle biopsies taken in the course of
11-h glutamine tracer infusion studies, it was shown that glutamine
baseline enrichment in muscle equaled that of plasma (van Acker et al. 1998
).
Analytical methods.
The biopsies were freeze-dried and further freed from adherent
blood and connective tissues. The water content of the biopsies was
calculated from the weight difference before and after
freeze-drying and used for conversion from dry to wet weight. The
muscle specimens were powdered and deproteinized using a
Mini-Beadbeater (Biospeck Products, Bartlesville, OK). Of the
pulverized tissue, ~30 mg was added to 400 µL sulfosalicylic acid
50 g/L and 0.1 g glass beads (diameter 1 mm; Biospeck Products)
and beaten for 50 s. The supernatant was frozen in liquid nitrogen
and stored at -80°C until later analysis. The concentration of
glutamine in supernatant, plasma and tracer infusate was determined by
fully automated HPLC (van Eijk et al. 1993
). Muscle intracellular
glutamine concentration was expressed per liter intracellular water
(Bergström et al. 1974
, Vinnars et al. 1975
).
The 15 N enrichment of plasma and muscle
glutamine was determined using a tert-butyldimethylsilyl
derivative and a gas chromatographic combustion isotope ratio mass
spectrometry (Finnigan MAT 252, Bremen, Germany), as previously
described (van Acker et al. 1998
). Plasma enrichments of
-ketoisocaproate (KIC) were measured using a
quinoxalinoltrimethylsilyl derivative and a gas
chromatographic-mass spectrometric system (Finnigan Incos XL, San
Jose, CA), in a similar manner to that described previously
(Ford et al. 1985
). Final values for KIC determinations
were corrected using calibration curves.
Calculations.
The Ra of glutamine into plasma
(Ra,gln, in µmol · kg-1 ·
h-1) was calculated as:
 |
where [i[15N]gln] is
the tracer infusion rate in µmol · kg-1 ·
h-1, Ei,gln is the
glutamine enrichment in the tracer infusate, expressed in mole
percentage excess (MPE), and Ep,gln is the mean
plasma glutamine enrichment between 2 and 6 h of tracer infusion.
As demonstrated before, the rate of glutamine appearance obtained in
this way overestimates the true appearance rate of glutamine in plasma
by at least 20% because of slow equilibration of the glutamine tracer
with the large muscle glutamine pool (van Acker et al. 1998
).
Proteolysis was measured using the whole body Ra
of leucine (Ra,leu in µmol ·
kg-1 · h-1).
Ra,leu was calculated using plasma KIC
enrichments (Horber et al. 1989
):
 |
where [i[13C]leu]is the tracer infusion rate in µmol · kg-1 · h-1, Ei,leu is the leucine enrichment (MPE) in the tracer infusate and Ep,KIC is the average plasma KIC enrichment from 2 to 6 h of tracer infusion. In the absence of exogenous amino acids, the calculated Ra by definition equals the endogenous Ra.
Glutamine arising from protein degradation
(PDgln) was calculated as:
 |
where 4.4 and 8 are the assumed glutamine and leucine contents
of body protein (g per 100 g of protein), respectively, and 146
and 131 are glutamine and leucine molecular weights (g/mol),
respectively (Kuhn et al. 1999
).
The intracellular concentration of glutamine [Gln]i was
calculated by subtracting the free extracellular part from the total
amount (Glnm), as previously described
(Bergström et al. 1974
):
 |
assuming the plasma concentration [Gln]p to be
equal to the concentration in the interstitial fluid. Regarding the
preoperative measurements, the extracellular
(H2Oe) and intracellular
(H2Oi) water content (mL/kg muscle) were
assumed to amount to 13 and 87% of the total water content of muscle
tissue (Bergström et al. 1974
). Concerning the
increased extracellular and decreased intracellular water content
observed after surgical trauma (Vinnars et al. 1975
),
values of 18% (H2Oe) and 82%
(H2Oi) were used for the measurements performed
on the second postoperative day. Values of intracellular enrichment
were calculated in a similar manner.
Statistics.
Data are given as means ± SEM, unless stated otherwise. Comparisons between pre- and postoperative values were made using the Wilcoxon matched pairs signed rank sum test. The Mann-Whitney U test was used for comparing data from different patient groups (i.e., patients with and without cancer, patients with and without epidural anesthesia). Regarding the time course of glutamine and KIC enrichment in plasma, a repeated measures ANOVA was performed to detect effects of time and surgical treatment. A P-value of <0.05 was considered significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
. A plateau in enrichment was achieved for KIC but not for glutamine.
Plasma glutamine enrichment increased slowly but significantly with
tracer infusion time (P < 0.05), indicating that
isotopic steady state had not been reached. Similar values were
obtained for pre- and postoperative glutamine enrichment in plasma. On
the other hand, plasma KIC enrichment decreased after surgery
(P < 0.001), reflecting increased dilution of the
leucine tracer by endogenous amino acids. When calculating whole body
protein breakdown rates, individual patients showed higher values on
the second postoperative day than during the preoperative study. On
average, leucine Ra increased by 26
± 5%, from 91 ± 3 µmol · kg-1
· h-1 before operation to 115 ± 6 µmol
· kg-1 · h-1 2 d
after surgery (Fig. 2
, P < 0.001). Despite the rise in whole body protein
breakdown, no increase was observed in the
Ra of glutamine in plasma (Fig. 3
). Whole body glutamine Ra in plasma averaged 246
± 8 and 241 ± 10 µmol · kg-1 ·
h-1 during the pre- and
postoperative measurement, respectively, with some patients showing no
change, some showing an increase and some a decrease in glutamine
Ra. The calculated amount of glutamine
Ra arising from proteolysis increased in each
patient, and averaged 45 ± 1 µmol ·
kg-1 · h-1 before and
57 ± 3 µmol · kg-1 ·
h-1 on d 2 after surgery (P < 0.001).
|
|
|
). Also, similar values were obtained in patients with recent weight
loss and patients with a stable weight. The presence of epidural
anesthesia did not affect the postoperative changes in leucine and
glutamine Ra: leucine
Ra increased by 30 ± 6% and 20
± 6% in the patients with and without epidural anesthesia,
respectively, whereas glutamine Ra did not
change in either group
(-4± 6% and -1 ± 3%).
|
,
P < 0.001). Hematocrit decreased by 12 ± 2%, from 0.40 ± 0.01 to 0.35 ± 0.01 (P
< 0.001), indicating that part of the reduction in plasma
glutamine may be attributed to postsurgical hemodilution. A decrease
also occurred in the concentration of intramuscular free glutamine:
from 10.82 ± 0.75 to 7.69 ± 0.59 mmol/L intracellular
water, a decline of 27 ± 6% (Fig. 5
, P < 0.01). No change was observed in the total
water content in muscle tissue: 759 ± 19 mL/kg muscle before
surgery vs.
756± 16 mL/kg muscle 2 d after surgery.
|
|
,
P < 0.05). When the postoperative reduction in the
size of the intramuscular free glutamine pool was taken into account,
similar amounts of labeled glutamine were found in muscle after 6 h of tracer infusion: 4.0 ± 0.6 and 4.1 ± 0.5 µmol/L
intracellular water during pre- and postoperative measurements,
respectively. As shown in Figure 6
, in four postoperative patients an
additional biopsy was taken ~3 h after start of tracer infusion. The
rate of rise of labeled glutamine in muscle calculated from the
consecutive biopsies was 0.56 ± 0.05 µmol · L intracellular
water-1 · h-1 between 3 and 6 h of
tracer infusion. When, in these patients, the rate of rise of labeled
glutamine in muscle was calculated on the basis of a single biopsy at
6 h assuming equal enrichment in plasma and muscle at baseline, a
similar value was obtained (0.58 ± 0.09 µmol · L
intracellular water-1 · h-1), suggesting
that the assumption was valid.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
, Vinnars et al. 1975
). The catabolic stress response was not arrested by
continuous epidural infusion of local anesthetics, presumably as a
result of the 60–70% lower dose of bupivacaine used in the present
study as compared to previous investigations on the effect of epidural
anesthesia (Carli et al. 1996
). Proteolysis of skeletal
muscle is a major contributor to the increase in whole body protein
breakdown observed 2 d after surgery (Clowes et al. 1983
). The decrease in the concentration of glutamine in
skeletal muscle is a highly consistent finding after trauma
(Essén et al. 1992
,Vinnars et al. 1975
). Quantitatively, this is a considerable reduction,
because muscle glutamine represents more than half of the total free
amino acid pool in the human body. Essén et al. observed a 21%
decline in the concentration of glutamine in muscle during the first
24 h after surgery (Essén et al. 1992
). This
would indicate that the losses of glutamine from the intracellular free
glutamine pool occur mainly during the first postoperative day, and to
a smaller extent during the following days.
The rise in protein breakdown and the shrinking plasma and
intracellular glutamine pools 48 h after laparotomy are consistent
with the concept of an increased metabolic demand of glutamine in the
postoperative period. Nevertheless, this remains conjectural because it
is not fully known how intracellular glutamine levels are maintained
and how this process is regulated. Other possibilities may include an
impairment of membrane integrity, a loss of the
Na+ electrochemical gradient and/or changes in
the activity of the glutamine transporter by trauma (Hundal et al. 1987
, Rennie et al. 1986
). Evidence exists
that tissues involved in the immune system, such as liver and spleen,
take up increased amounts of glutamine in response to trauma
(Deutz et al. 1992
). Previous studies in humans have
shown an increased net release of glutamine from muscle during periods
of elevated metabolic stress, such as during sepsis (Clowes et al. 1980
), 3 to 5 d after major trauma (Clowes et al. 1980
), immediately after elective cholecystectomy
(Stjernström et al. 1986
), 4 d after
hysterectomy (Carli et al. 1990
) and on the d 2 after
elective gastrointestinal surgery in a group of patients similar as the
present study group (Mjaaland et al. 1993
). On the other
hand, utilizing tracer kinetic techniques, we did not observe a rise in
the Ra of glutamine in plasma 2 d after
surgery. Our findings are in agreement with a recent study in
critically ill patients, showing an unaltered plasma glutamine
Ra when compared to matched healthy controls,
despite a major increase in proteolysis and decrease in plasma
glutamine concentration (Jackson et al. 1999
). A
discrepancy between the Ra of glutamine in
plasma and the net release of glutamine from muscle has previously been
observed in our laboratory: in rats, the surgery-induced rise in
the net release of muscle glutamine was not matched by an increased
plasma Ra (de Blaauw et al. 1998
).
In the absence of exogenous glutamine, the sources that contribute to
the Ra of glutamine are proteolysis, de
novo synthesis and glutamine losses from the free intracellular
pool. Because glutamine derived from proteolysis was increased after
surgery, a decline in the rate of glutamine de novo
synthesis and/or a reduction in the loss from the free intracellular
pool are factors that might explain the absence of any change in the
whole body glutamine Ra. Hankard et al. recently
observed an ~11% decline in whole-body glutamine
Ra between 18 and 42 h of fasting, entirely
accounted for by a drop in the estimated rates of glutamine de
novo synthesis (Hankard et al. 1997
). In the
present study, the preoperative measurements were conducted after an
overnight fast, whereas during the postsurgical measurements patients
were in a near-fasted state for about 80 h. Only a limited
amount of glucose was provided in the immediate postoperative days,
which is the postoperative clinical routine in patients undergoing
gastrointestinal surgery. In theory, therefore, this period of fasting
may have played a role in our observation that the plasma
Ra of glutamine was not increased on the second
postoperative day.
Although skeletal muscle is the main glutamine-producing tissue
[in humans >60% of endogenous glutamine Ra is
released by muscle (Nurjhan et al. 1995
, Stumvoll et al. 1996
)], other sources such as liver, brain, lung and
adipose tissue also contribute to the Ra of
glutamine in plasma measured by tracer dilution techniques. An
alternative explanation for the unchanged whole body glutamine
Ra after laparotomy, therefore, is that any
surgery-induced rise in muscle glutamine release might have been
offset by a decreased release from sources other than muscle, such as
liver. Increased consumption of glutamine produced within the tissue
itself, before exchange has occurred with the systemic circulation, may
contribute to the diminished release. In a previous study in pigs, we
showed that the liver switches from net production of glutamine in the
preoperative setting to net consumption of glutamine after surgery
(Deutz et al. 1992
). Part of the glutamine consumed by
the liver may be used for proliferation of Kupffer cells and synthesis
of acute phase proteins, another part for gluconeogenesis.
With respect to the muscle data, we assumed similar glutamine baseline
enrichment values in muscle and plasma. Support for this assumption
comes from the consecutive muscle biopsies taken here and in a previous
study (van Acker et al. 1998
). By extrapolating the successive
glutamine enrichment data back to time zero, it was shown that the
baseline enrichment in muscle approximated that in plasma, both in pre-
and postoperative patients. As a result of the slow equilibration of
the glutamine tracer with the large muscle glutamine pool, the
Ra of glutamine in plasma overestimates the
whole-body glutamine flux (van Acker et al. 1998
). In this study,
too, isotopic steady-state conditions were not achieved during the
6-h infusion of glutamine tracers, neither before nor after surgery.
However, similar amounts of glutamine tracer were retained in the
intramuscular free glutamine pool during the two measurements, i.e.,
before and 2 d after surgery. This indicates that the degree in
which the true glutamine flux is overestimated by the measured
glutamine Ra probably is of the same magnitude
for both pre- and postoperative measurements.
In conclusion, plasma and muscle glutamine concentrations are decreased in patients 48 h after laparotomy. These findings have been suggested to result from increased uptake by the immune system. An increased plasma glutamine Ra was not shown in our patients, despite the fact that previous studies in animal models and humans have shown an increased net release of glutamine from muscle following trauma or infection. One of the explanations for the absence of an increase in plasma glutamine Ra may be a decreased release from nonmuscular tissues (e.g., liver) or a decreased de novo synthesis of glutamine in muscle. Further research is warranted to elucidate whether absence of an increase in the plasma glutamine Ra of these patients provides a rationale for glutamine supplementation. A reduction in the de novo synthesis of glutamine may reflect shortage of substrate for glutamine synthesis in muscle (e.g., glutamate and muscle protein derived amino acids). In that case it is likely that patients undergoing gastrointestinal surgery will benefit from glutamine supplementation in the first few days after surgery.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
3 Abbreviations used: KIC, -ketoisocaproate; MPE, mole percentage excess; Ra, rate of appearance.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. Ardawi M. S., Newsholme E. A. Glutamine metabolism in lymphocytes of the rat. Biochem. J. 1983;212:835-842[Medline]
2.
Bergström J., Fürst P., Norée L.-O., Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J. Appl. Physiol. 1974;36:693-697
3. Cao Y., Feng Z., Hoos A., Klimberg V. S. Glutamine enhances gut glutathione production. J. Parent. Ent. Nutr. 1998;22:224-227
4. Carli F., Phil M., Halliday D. Modulation of protein metabolism in the surgical patient: effect of 48-hour continuous epidural block with local anesthetics on leucine kinetics. Reg. Anesth. 1996;21:430-435[Medline]
5. Carli F., Webster J., Ramachandra V., Pearson M., Read M., Ford G. C., McArthur S., Preedy V. R., Halliday D. Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support. Clin. Sci. 1990;78:621-628[Medline]
6. Clowes G. H. A. Jr, George B. C., Villee C. A., Saravis C. A. Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. N. Eng. J. Med. 1983;308:545-552[Abstract]
7. Clowes G. H. A. Jr, Randall H. T., Cha C.-J. Amino acid and energy metabolism in septic and traumatized patients. J. Parent. Ent. Nutr. 1980;4:195-203
8. de Blaauw I., Deutz N. E. P., von Meyenfeldt M. F. Cancer reduces the metabolic response of muscle to surgical stress in the rat. J. Surg. Res. 1998;80:94-101[Medline]
9. Deutz N. E. P., Reijven P. L. M., Athanasas G., Soeters P. B. Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. Clin. Sci. 1992;83:607-614[Medline]
10.
Dietrichson P., Coakley J., Smith P. E. M., Griffiths R. D., Helliwell T. R., Edwards R. H. T. Conchotome and needle percutaneous biopsy of skeletal muscle. J. Neurol. Neurosur. Ps. 1987;50:1461-1467
11. Douglas R. G., Shaw J. H. F. Metabolic response to sepsis and trauma. Br. J. Surg. 1989;76:115-122[Medline]
12. Essén P., Wernerman J., Sonnenfeld T., Thunell S., Vinnars E. Free amino acids in plasma and muscle during 24 hours post-operatively —a descriptive study. Clin. Physiol. 1992;12:163-177[Medline]
13. Ford G. C., Cheng K. N., Halliday D. Analysis of [1-13C]KIC in plasma by capillary gas chromatography/mass spectrometry in protein turnover studies. Biomed. Mass. Spectrom. 1985;12:432-436[Medline]
14. Halperin M. L., Ethier J. H., Kamel K. S. The excretion of ammonium ions and acid base balance. Clin. Biochem. 1990;23:185-188[Medline]
15. Hankard R. G., Haymond M. W., Darmaun D. Role of glutamine as a glucose precursor in fasting humans. Diabetes 1997;46:1535-1541[Abstract]
16.
Horber F., Horber-Feyder C., Krayer S., Schwenk W., Haymond M. Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis. Am. J. Physiol. 1989;257:E385-E399
17.
Hundal H. S., Rennie M. J., Watt P. W. Characteristics of L-glutamine transport in perfused rat skeletal muscle. J. Physiol. 1987;393:283-305
18.
Jackson N. C., Caroll P. V., Russell-Jones D. L., Sönksen P. H., Treacher D. F., Umpleby A. M. The metabolic consequences of critical illness: acute effects on glutamine and protein metabolism. Am. J. Physiol. 1999;276:E163-E170
19.
Kuhn K. S., Schuhmann K., Stehle P., Darmaun D., Fürst P. Determination of glutamine muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production. Am. J. Clin. Nutr. 1999;70:484-489
20. Lacey J. M., Wilmore D. W. Is glutamine a conditionally essential amino acid?. Nutr. Rev. 1990;48:297-309[Medline]
21. Mjaaland M., Unneberg K., Larsson J., Nilsson L., Revhaug A. Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3-methylhistidine and total amino acid efflux in patients receiving total parenteral nutrition. Ann. Surg. 1993;217:413-422[Medline]
22. Nurjhan N., Bucci A., Periello G., Stumvoll M., Dailey G., Bier D.M., Toft I., Jenssen T. G., Gerich J. E. Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man. J. Clin. Invest. 1995;95:272-277
23. Rennie M. J., Hundal H. S., Babij P., MacLennan P., Taylor P. M., Watt P. W., Jepson M. M., Milward D. J. Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. Lancet 1986;2:1008-1012[Medline]
24. Stjernström H., Lund J., Wiklund L., Bergholm U., Vinnars E., Hamberger B., Jorfeldt L. The influence of abdominal surgical trauma on the exchange of blood –borne amino acids in the human leg. Clin. Nutr. 1986;5:123-131
25. Stumvoll M., Periello G., Nurjhan N., Buci A., Welle S., Jansson P.-A., Dailey G., Bier D., Jenssen T., Gerich J. Glutamine and alanine metabolism in NIDDM. Diabetes 1996;45:863-868[Abstract]
26. van Acker B. A. C., Hulsewé K. W. E., Wagenmakers A. J. M., Deutz N. E. P., van Kreel B. K., Halliday D., Matthews D. E., Soeters P. B., von Meyenfeldt M. F. Absence of glutamine isotopic steady state: implications for the assessment of whole body glutamine production rate. Clin. Sci. 1998;95:339-346[Medline]
27. van Eijk H. M. H., Dejong C. H. C., Deutz N. E. P., Soeters P. B. Influence of storage conditions on normal plasma amino-acid concentrations. Clin. Nutr. 1994;13:374-380
28. van Eijk H. M. H., Rooyackers D. R., Deutz N. E. P. Rapid routine determination of amino acids in plasma by high-performance liquid chromatography with a 2–3 µM Spherisorb ODS II column. J. Chrom. 1993;620:143-148
29. Vinnars E., Bergström J., Fürst P. Influence of the postoperative state on the intracellular free amino acids in human muscle tissue. Ann. Surg. 1975;182:665-671[Medline]
30.
Wannemacher R. W. Jr Key role of various individual amino acids in host response to infection. Am. J. Clin. Nutr. 1977;30:1269-1280
31. Windmueller H. G. Glutamine utilization by the small intestine. Adv. Enzymol. 1982;53:201-237
This article has been cited by other articles:
|
|
 |
|
  J. Wernerman Clinical Use of Glutamine Supplementation J. Nutr., October 1, 2008; 138(10): 2040S - 2044S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C Ligthart-Melis, M. C. van de Poll, P. G Boelens, C. H. Dejong, N. E. Deutz, and P. A. van Leeuwen Glutamine is an important precursor for de novo synthesis of arginine in humans Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1282 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Ligthart-Melis, M. C. G. van de Poll, C. H. C. Dejong, P. G. Boelens, N. E. P. Deutz, and P. A. M. van Leeuwen The Route of Administration (Enteral or Parenteral) Affects the Conversion of Isotopically Labeled L-[2-15N]Glutamine Into Citrulline and Arginine in Humans JPEN J Parenter Enteral Nutr, September 1, 2007; 31(5): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. G. van de Poll, G. C. Ligthart-Melis, P. G. Boelens, N. E. P. Deutz, P. A. M. van Leeuwen, and C. H. C. Dejong Intestinal and hepatic metabolism of glutamine and citrulline in humans J. Physiol., June 1, 2007; 581(2): 819 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Koopman, D. L. E. Pannemans, A. E. Jeukendrup, A. P. Gijsen, J. M. G. Senden, D. Halliday, W. H. M. Saris, L. J. C. van Loon, and A. J. M. Wagenmakers Combined ingestion of protein and carbohydrate improves protein balance during ultra-endurance exercise Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E712 - E720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Soeters, M. C. G. van de Poll, W. G. van Gemert, and C. H. C. Dejong Amino Acid Adequacy in Pathophysiological States J. Nutr., June 1, 2004; 134(6): 1575S - 1582S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Lobley, S. O. Hoskin, and C. J. McNeil Glutamine in Animal Science and Production J. Nutr., September 1, 2001; 131(9): 2525S - 2531. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.05. MPE, mole percentage excess.
