|
The role of dehydroepiandrosterone in AIDS
Centurelli M.A.; Abate M.A.
M.A. Centurelli, Department of Pharmacy, New England Medical
Center, Box 420, 750 Washington St., Boston, MA 02111 United
States
Annals of Pharmacotherapy (United States) 1997, 31/5
(639-642)
The use of DHEA for the treatment of AIDS shows some
promise, although controlled trials have not been performed to
evaluate its efficacy. Low serum concentrations of DHEA have
been correlated with states of decreased immune function in
humans, since concentrations are lowest in early childhood,
late adulthood, and as HIV disease progresses. DHEA appears to
possess immunomodulating effects, perhaps by enhancing the
secretion of IL-2 from activated T cells as demonstrated in a
murine model. A decline in DHEA concentrations, particularly
when initially less than 2.01 mug/L, might also prove to be a
predictor of HIV disease progression. It is also plausible
that a decrease in DHEA concentrations can be used to predict
a decline in overall health status. Although the role of DHEA
in the treatment of AIDS has not yet been determined, the drug
appears to show potential for clinical benefit that should be
evaluated in large, randomized, controlled trials.
Replacement of DHEA in aging men and women.
Potential remedial effects
Yen S.S.C.; Morales A.J.; Khorram O.
Dept of Reproductive Medicine, University of California, San
Diego,La Jolla, CA 92093 U S
Annals of the New York Academy of Sciences (United States)
1995, 774/- (128-142)
DHEA in appropriate replacement doses appears to have
remedial effects with respect to its ability to induce an
anabolic growth factor, increase muscle strength and lean body
mass, activate immune function, and enhance quality of life in
aging men and women, with no significant adverse effects.
Further studies are needed to confirm and extend our current
results, particularly the gender differences.
Coenzyme Q10 treatment in mitochondrial
encephalomyopathies. Short-term double-blind, crossover
study.
Chen RS; Huang CC; Chu NS
Dept of Neurology, Chang Gung Medical College and Memorial
Hospital, Taipei, Taiwan
Eur Neurol (Switzerland) 1997, 37 (4) p212-8
We report a short-term double-blind, crossover study of
CoQ10 in 8 patients with mitochondrial encephalomyopathies.
Four patients had myoclonus epilepsy with ragged-red fibers
syndrome, 3 had mitochondrial myopathy, encephalopathy, lactic
acidosis and stroke-like episodes syndrome, and 1 had chronic
progressive external ophthalmoplegia with myopathy. A trend of
effectiveness of CoQ10 in several parameters was noted.
Fatigability of daily activities was alleviated. The endurance
to muscle exercise was augmented. Global muscle strength
scored by Medical Research Council scale was increased. The
extent of elevation in serum lactate and pyruvate levels after
exercise was decreased. However, only the global MRC index
score had a statistical significance (p < 0.05). There were
no side effects during therapy. The serum CoQ10 levels were
significantly lower in patients than in normal controls before
CoQ10 treatment and increased significantly after
treatment.
Effects of L-carnitine on the pyruvate
dehydrogenase complex and carnitine palmitoyl transferase
activities in muscle of endurance athletes.
Arenas J; Huertas R; Campos Y; Diaz AE; Villalon JM; Vilas
E
Centro de Investigacion, Hospital 12 de Octubre, Madrid,
Spain.
FEBS Lett (Netherlands) Mar 14 1994, 341 (1)
p91-3
The effects of L-carnitine on the pyruvate dehydrogenase
(PDH) complex and carnitine palmitoyl transferase (CPT) were
studied in muscle of 16 long-distance runners (LDR). These
subjects received placebo or L-carnitine (2 g orally) during a
4-week period of training. Athletes receiving L-carnitine
showed a dramatic increase (P < 0.001) in the PDH complex
activities. By contrast, the levels of CPT, both 1 and 2, were
unchanged. No significant changes were observed after placebo
administration. We previously reported [Huertas R. et al.,
Biochem. Biophys. Res. Commun. 188 (1992) 102-107] that
L-carnitine induces an increase in the activities of complexes
I, III and IV of the respiratory chain in muscle of LDR. Taken
together, our data suggest that the improvement in (maximal
oxygen consumption) VO2max observed in LDR after L-carnitine
administration is based on these biochemical findings.
Plasma lipid concentrations in hyperlipidemic
patients consuming a high-fat diet supplemented with pyruvate
for 6 wk.
Stanko RT; Reynolds HR; Lonchar KD; Arch JE
Clinical Nutrition Unit, Montefiore University Hospital,
Pittsburgh, PA 15213.
Am J Clin Nutr (United States) Nov 1992, 56 (5)
p950-4
We evaluated the effects of a three-carbon compound,
pyruvate, on plasma lipid concentrations in hyperlipidemic
patients consuming a high-cholesterol (560-620 mg), high-fat
(45-47% of energy; 18-20% of energy as saturated fatty acid),
anabolic diet (0.11-0.12 MJ/kg body wt) for 6 wk. Forty
subjects consumed the diet, randomly supplemented with 36-53 g
pyruvate (n = 19) or 21-37 g polyglucose (placebo, Polycose, n
= 21) as a portion of carbohydrate energy. Plasma cholesterol
and LDL-cholesterol concentrations were unchanged in the
placebo group, but decreased by 4% and 5%, respectively, in
the pyruvate group (P < 0.05 vs placebo). Plasma
HDL-cholesterol, HDL3-cholesterol, and triglyceride
concentrations were similar in both groups. Resting heart
rate, diastolic blood pressure, and rate-pressure product were
unchanged after 6 wk of therapy in the placebo group, but
decreased by 9%, 6%, and 12%, respectively with pyruvate
supplementation (P < 0.05 vs placebo). We conclude that
pyruvate supplementation of a high-fat, high-cholesterol,
anabolic diet will decrease plasma cholesterol and
LDL-cholesterol concentrations without affecting the
HDL-cholesterol concentration.
Enhanced leg exercise endurance with a
high-carbohydrate diet and dihydroxyacetone and
pyruvate.
Stanko RT; Robertson RJ; Galbreath RW; Reilly JJ Jr;
Greenawalt KD; Goss FL
Department of Medicine, Montefiore University Hospital,
Pittsburgh, Pennsylvania.
J Appl Physiol (United States) Nov 1990, 69 (5)
p1651-6
The effects of dietary supplementation of dihydroxyacetone
and pyruvate (DHAP) on metabolic responses and endurance
capacity during leg exercise were determined in eight
untrained males (20-30 yr). During the 7 days before exercise,
a high-carbohydrate diet was consumed (70% carbohydrate, 18%
protein, 12% fat; 35 kcal/kg body weight). One hundred grams
of either Polycose (placebo) or dihydroxyacetone and pyruvate
(treatment, 3:1) were substituted for a portion of
carbohydrate. Dietary conditions were randomized, and subjects
consumed each diet separated by 7-14 days. After each diet,
cycle ergometer exercise (70% of peak oxygen consumption) was
performed to exhaustion. Biopsy of the vastus lateralis muscle
was obtained before and after exercise. Blood samples were
drawn through radial artery and femoral vein catheters at
rest, after 30 min of exercise, and at exercise termination.
Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and
DHAP, respectively (P less than 0.01). Muscle glycogen at rest
and exhaustion did not differ between diets. Whole leg
arteriovenous glucose difference was greater (P less than
0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs.
0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14
vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma
free fatty acids, glycerol, and beta-hydroxybutyrate were
similar during rest and exercise for both diets. Estimated
total glucose oxidation during exercise was 165 +/- 17 and 203
+/- 15 g after placebo and DHAP, respectively (P less than
0.05). It is concluded that feeding of DHAP for 7 days in
conjunction with a high carbohydrate diet enhances leg
exercise endurance capacity by increasing glucose extraction
by muscle.
Fat metabolism in exercise
Wolfe R.R.
R.R. Wolfe, Univ. of Texas Med. Branch Galveston, Shriners
Bums Institute, Metabolism Unit, 815 Market Street, Galveston,
TX 77550 United States
Advances in Experimental Medicine and Biology (United States)
1998, 441/- (147-156)
Fatty acids are the most abundant source of endogenous
energy substrate. They can be mobilized from peripheral
adipose tissue and transported via the blood to active muscle.
During higher intensity exercise, triglyceride within the
muscle can also be hydrolyzed to release fatty acids for
subsequent direct oxidation. Control of fatty acid oxidation
in exercise can potentially occur via changes in availability,
or via changes in the ability of the muscle to oxidize fatty
acids. We have performed a series of experiments to
distinguish the relative importance of these potential sites
of control. The process of lipolysis normally provides free
fatty acids (FFA) at a rate in excess of that required to
supply resting energy requirements. At the start of low
intensity exercise, lipolysis increases further, thereby
providing sufficient FFA to provide energy substrates in
excess of requirements. However, lipolysis does not increase
further as exercise intensity increases, and fatty acid
oxidation becomes approximately equal to the total amount of
fatty acids available at 65% of VOinf 2 max. When plasma FFA
concentration is increased by lipid infusion during exercise
at 85% VOinf 2 max, fat oxidation is significantly increased.
Taken together, these observations indicate that fatty acid
availability can be a determinant of the rate of their
oxidation during exercise. However, even when lipid is infused
well in excess of requirements during high-intensity exercise,
less than half the energy is derived from fat. This is because
the muscle itself is a major site of control of the rate of
fat oxidation during exercise. We have demonstrated that the
mechanism of control of fatty acid oxidation in the muscle is
the rate of entry into the mitochondria. We hypothesize that
the rate of glycolysis is the predominant regulator of the
rate of carbohydrate metabolism in muscle, and that a rapid
rate of carbohydrate oxidation caused by mobilization of
muscle glycogen during high intensity exercise inhibits fatty
acid oxidation by limiting transport into the mitochondria.
During low intensity exercise, glycogen breakdown and thus
glycolysis is not markedly stimulated, so the increased
availability of fatty acids allows their oxidation to serve as
the predominant energy source. At higher intensity exercise,
stimulation of glycogen breakdown and glycolysis cause
increased pyruvate entry into the TCA cycle for oxidation, and
as a consequence the inhibition of fatty acid oxidation by
limiting their transport into the mitochondria.
Coenzyme Qinf 1inf 0 treatment in mitochondrial
encephalomyopathies. Short-term double-blind, crossover
study
Chen R.-S.; Huang C.-C.; Chu N.-S.
C.-C. Huang, Department of Neurology, Chang Gung Memorial
Hospital, 199 Tung Hwa North Road, Taipei Taiwan
European Neurology (Switzerland) 1997, 37/4
(212-218)
We report a short-term double-blind, crossover study of
CoQinf 1inf 0 in 8 patients with mitochondrial
encephalomyopathies. Four patients had myoclonus epilepsy with
ragged-red fibers syndrome, 3 had mitochondrial myopathy,
encephalopathy, lactic acidosis and stroke-like episodes
syndrome, and 1 had chronic progressive external
ophthalmoplegia with myopathy. A trend of effectiveness of
CoQinf 1inf 0 in several parameters was noted. Fatigability of
daily activities was alleviated. The endurance to muscle
exercise was augmented. Global muscle strength scored by
Medical Research Council scale was increased. The extent of
elevation in serum lactate and pyruvate levels after exercise
was decreased. However, only the global MRC index score had a
statistical significance (p < 0.05). There were no side
effects during therapy. The serum CoQinf 1inf 0 levels were
significantly lower in patients than in normal controls before
CoQinf 1inf 0 treatment and increased significantly after
treatment.
Low plasma glutamine in combination with high
glutamate levels indicate risk for loss of body cell mass in
healthy individuals: the effect of N-acetyl-cysteine.
Kinscherf R; Hack V; Fischbach T; Friedmann B; Weiss C; Edler
L; Bartsch P; Droge W
Division of Immunochemistry, Deutsches
Krebsforschungszentrum, Heidelberg, Germany.
J Mol Med (Germany) Jul 1996, 74 (7) p393-400
Skeletal muscle catabolism, low plasma glutamine, and high
venous glutamate levels are common among patients with cancer
or human immunodeficiency virus infection. In addition, a high
glycolytic activity is commonly found in muscle tissue of
cachectic cancer patients, suggesting insufficient
mitochondrial energy metabolism. We therefore investigated (a)
whether an "an-aerobic physical exercise" program causes
similar changes in plasma amino acid levels, and (b) whether
low plasma glutamine or high glutamate levels are risk factors
for loss of body cell mass (BCM) in healthy human subjects,
i.e., in the absence of a tumor or virus infection.
Longitudinal measurements from healthy subjects over longer
periods suggest that the age-related loss of BCM occur mainly
during episodes with high venous glutamate levels, indicative
of decreased muscular transport activity for glutamate. A
significant increase in venous glutamate levels from 25 to
about 40 microM was seen after a program of "anaerobic
physical exercise." This was associated with changes in T
lymphocyte numbers. Under these conditions persons with low
baseline levels of plasma glutamine, arginine, and cystine
levels also showed a loss of BCM. This loss of BCM was
correlated not only with the amino acid levels at baseline
examination, but also with an increase in plasma glutamine,
arginine, and cystine levels during the observation period,
suggesting that a loss of BCM in healthy individuals
terminates itself by adjusting these amino acids to higher
levels that stabilize BCM. To test a possible regulatory role
of cysteine in this context we determined the effect of
N-acetyl-cysteine on BCM in a group of subjects with
relatively low glutamine levels. The placebo group of this
study showed a loss of BCM and an increase in body fat,
suggesting that body protein had been converted into other
forms of chemical energy. The decrease in mean BCM/body fat
ratios was prevented by N-acetyl-cysteine, indicating that
cysteine indeed plays a regulatory role in the physiological
control of BCM.
Glutamine metabolism and transport in skeletal
muscle and heart and their clinical relevance.
Rennie MJ; Ahmed A; Khogali SE; Low SY; Hundal HS; Taylor
PM
Department of Anatomy and Physiology, University of Dundee,
Scotland, United Kingdom.
J Nutr (United States) Apr 1996, 126 (4 Suppl)
p1142S-9S
The glutamine and glutamate transporters in skeletal muscle
and heart appear to play a role in control of the steady-state
concentration of amino acids in the intracellular space and,
in the case of skeletal muscle at least, in the rate of loss
of glutamine to the plasma and to other organs and tissues.
This article reviews what is currently known about transporter
characteristics and mechanisms in skeletal muscle and heart,
the alterations in transport activity in pathophysiological
conditions and the implications for anabolic processes and
cardiac function of altering the availability of glutamine .
The possibilities that glutamine pool size is part of an
osmotic signaling mechanism to regulate whole body protein
metabolism is discussed and evidence is shown from work on
cultured muscle cells. The possible uses of glutamine in
maintaining cardiac function perioperatively and in promoting
glycogen metabolism are discussed. (33 Refs.)
Lung glutamine flux following open heart
surgery.
Herskowitz K; Plumley DA; Martin TD; Hautamaki RD; Copeland
EM 3d; Souba WW
Department of Surgery, University of Florida College of
Medicine, Gainesville 32601.
J Surg Res (United States) Jul 1991, 51 (1)
p82-6
Despite the attenuated skeletal muscle proteolysis that
occurs following hypothermic anesthesia and open heart
surgery, blood amino acid levels are maintained, suggesting
enhanced amino acid release by another organ. To investigate
the role of the lung in this response, we determined the
release of glutamine (Gln) and alanine by the lung, since
these two amino acids transport two-thirds of circulating
amino acid nitrogen. Three groups of patients were studied:
(a) preoperative non-stressed controls; (b) postoperative
general surgical patients; and (c) postoperative cardiac
surgical patients studied on Postoperative Day 1 following
open heart surgery requiring cardiopulmonary bypass and
hypothermic anesthesia. In preoperative controls the lung was
an organ of glutamine and alanine balance. These exchange
rates were unaffected by the stress of an abdominal surgical
procedure despite a mild increase in pulmonary blood flow.
However, lung Gln release in the cardiac surgical patients was
significantly increased (-0.6 +/- 1.2 mumole/kg/min in
controls vs -6.5 +/- 1.3 mumole/kg/min in postoperative
hearts, P less than 0.05) and was due exclusively to an
increase in the pulmonary artery-systemic arterial
concentration difference. Alanine release by the lungs was
also increased in the postoperative cardiac surgical patients.
The mechanism by which this augmented pulmonary glutamine
release occurs following open heart surgery is unclear, but
the lungs appear to play a central role in maintaining amino
acid homeostasis. This metabolic role of the lungs following
hypothermic anesthesia and cardiopulmonary bypass has not been
previously described.
Absorption and metabolic effects of enterally
administered glutamine in humans.
Dechelotte P; Darmaun D; Rongier M; Hecketsweiler B; Rigal O;
Desjeux JF
Inst.Nat. de la Sante et de la Recherche Medicale Unite 290,
Hopital Saint-Lazare, Paris, France.
Am J Physiol (United States) May 1991, 260 (5 Pt 1)
pG677-82
To assess absorption and metabolic effects of enterally
delivered glutamine, a total of 10 healthy subjects received
perfusions of natural L- glutamine at graded infusion rates
(ranging from 0 to 126 mmol/h; n = 2-8 subjects at each rate)
along with a nonabsorbable marker (polyethylene glycol)
through a double-lumen nasojejunal tube. Perfusions were
administered after an overnight fast during three consecutive
1- or 2.5-h periods and in a randomized order. In eight
subjects, continuous intravenous infusion of
D-[6,6-2H2]glucose, L-[1-13C]leucine, and L-[15N]alanine was
simultaneously performed. Glutamine was nearly quantitatively
absorbed over the 30-cm study segment; estimated Km and Vmax
of glutamine absorption were 2.48 and 2.32 mmol/min over the
30-cm study segment. Enteral glutamine administration induced
1) a dose-dependent increase in plasma glutamine level; 2) a
rise in the plasma level and appearance rate (Ra) of alanine
(from 191 +/- 42 to 213 +/- 51 mumols.kg-1.h-1, P less than
0.05, for 0 and 46.8-mmol/h glutamine infusion rates,
respectively) and in plasma levels of glutamate, citrulline,
aspartate, and urea; 3) a decline in plasma free fatty acid
and glycerol levels; and 4) no change in leucine or glucose
Ra. We conclude that glutamine is efficiently absorbed by
human jejunum in vivo and may directly inhibit lipolysis,
whereas it neither affects proteolysis nor glucose production
in healthy postabsorptive humans.
Role of glutamine and its analogs in posttraumatic
muscle protein and amino acid metabolism.
Vinnars E; Hammarqvist F; von der Decken A; Wernerman J
Department of Anesthesiology, St Goran's Hospital, Stockholm,
Sweden.
J Parenter Enteral Nutr (U S) Jul-Aug 1990, 14 (4 Suppl)
p125S-129S
Skeletal muscle protein catabolism following trauma has
until recently not been possible to counteract by intravenous
nutritional means. The obligatory loss of nitrogen with
concomitant reduction of skeletal muscle protein synthesis is
also accompanied by a decrease of muscle free glutamine, the
extent of which is proportional to the muscle protein
catabolism. Serving as a human model of surgical trauma,
patients undergoing elective cholecystectomy were given total
parenteral nutrition including additions of either glutamine
or its analogs (ornithine-alpha-ketoglutarate,
alpha-ketoglutarate, or alanylglutamine) during 3
postoperative days. The polyribosome concentration and the
intracellular glutamine concentration in skeletal muscle, as
well as nitrogen balance, showed a less pronounced skeletal
muscle catabolism in these groups than when conventional total
parenteral nutrition was given. It is concluded that a support
of either glutamine or its carbon skeleton,
alpha-ketoglutarate, counteracts the postoperative fall of
muscle free glutamine and of muscle protein synthesis.
Furthermore, statistical correlations could be shown between
the changes of muscle glutamine and muscle protein synthesis
and the postoperative nitrogen losses.
Influence of enterectomy on peripheral tissue
glutamine efflux in critically ill patients.
Fong YM; Tracey KJ; Hesse DG; Albert JD; Barie PS; Lowry
SF
Department of Surgery, New York Hospital-Cornell Medical
Center, New York 10021.
Surgery (United States) Mar 1990, 107 (3) p321-6
Glutamine and alanine are dominant nitrogen carriers from
skeletal muscle stores to splanchnic organs. In addition,
these amino acids may also serve as a primary energy source
for the gastrointestinal tract during injury. To investigate
these contributions, we studied extremity amino acid efflux
during hypocaloric dextrose feedings and during total
parenteral nutrition in a population of normal volunteers (NL
VOL) (n = 9), a group of patients with sepsis who had
undergone laparotomy without bowel resection and were in the
intensive care unit (ICU) (n = 7), and patients with sepsis
after laparotomy (PT) (n = 2) who had recently undergone
greater than 80% bowel resection. Circulating alanine and
glutamine levels were significantly lower in the patients
compared with NL VOL under both feeding conditions. The
peripheral output of alanine was higher in the ICU group than
in the NL VOL during hypocaloric feedings. Glutamine efflux,
however, was independent of either the counterregulatory
hormone or substrate background. By contrast, enterectomy was
associated with a marked decrease of extremity glutamine
efflux compared with NL VOL or the ICU patients who did not
undergo enterectomy (-62 +/- 9 nmol/min/dl tissue in the PT vs
-265 +/- 32 nmol/min/dl tissue in the NL VOL and -311 +/- 58
nmol/min/dl tissue in the ICU group) during the dextrose
feedings; this difference persisted during subsequent total
parenteral nutrition (+12 +/- 13 nmol/min/dl tissue in PT vs
-178 +/- 56 nmol/min/dl tissue in the NL VOL and -287 +/- 81
nmol/min/dl tissue in the ICU group). These data suggest that
distinct mechanisms regulate peripheral alanine and glutamine
balance and that the gastrointestinal tract provides a
feedback signal to peripheral tissues to maintain glutamine
mobilization under both nonstressed and stressed
conditions.
Addition of glutamine to total parenteral nutrition
after elective abdominal surgery spares free glutamine in
muscle, counteracts the fall in muscle protein synthesis and
improves nitrogen balance.
Hammarqvist F; Wernerman J; Ali R; von der Decken A; Vinnars
E
Department of Surgery, St. Goran's Hospital, Stockholm,
Sweden.
Ann Surg (United States) Apr 1989, 209 (4)
p455-61
Twenty-two patients undergoing elective abdominal surgery
were given total parenteral nutrition (TPN) after the
operation. The TPN contained either a conventional amino acid
solution supplemented with glutamine or a conventional amino
acid solution without supplementation. To study amino acid and
protein metabolism, muscle biopsy specimens were taken before
surgery and on the third postoperative day. The postoperative
decrease in the intracellular concentration of free glutamine
was less pronounced in the glutamine group (21.8 +/- 5.5%)
than in the control group (38.7 +/- 5.1%; p less than 0.05).
The protein synthesis was reflected in the concentration and
size distribution of ribosomes. No significant changes in
these parameters were seen in the glutamine group after the
operation. In the control group, the total concentration of
ribosomes fell by 27.2 +/- 8.5% (p less than 0.05), and the
relative proportion of polyribosomes fell by 10.6 +/- 2.9% (p
less than 0.01). Although there were significant changes in
the control group, no significant differences in the changes
of these parameters between the two groups were detected. The
cumulative nitrogen loss was significantly less in the
glutamine group as compared to the control group during the
period studied--2.3 +/- 1.4 g versus 8.5 +/- 1.5 g,
respectively (p less than 0.01). Administration of glutamine
to catabolic patients is advocated.
Glutamine: a major energy source for cultured
mammalian cells.
Zielke HR; Zielke CL; Ozand PT
Fed Proc (United States) Jan 1984, 43 (1) p121-5
Cultured mammalian cells have two primary mechanisms for
obtaining energy necessary for growth: carbohydrate metabolism
to lactate and glutamine oxidation to CO2. In tissue culture
medium containing both glucose and glutamine, the contribution
of glutamine oxidation to the energy requirement ranges
between 30 and 50%. As the glucose concentration is decreased,
or when glucose is replaced by other carbohydrates, the rate
of glutamine oxidation increases and glutamine becomes the
sole energy source for cultured cells. The rate of glutamine
oxidation is regulated by the presence of glucose. The
apparent absolute requirement for glucose or other
carbohydrates in tissue culture medium is related to its role
in anabolic reactions rather than in energy production.
Oxidation of glucose, fatty acids, or ketone bodies does not
contribute significantly to the energy needs of cultured
mammalian cells. The data also suggest that consideration
should be given to glutamine as an important energy source in
vivo.
Glutamine: Effects on the immune system, protein
metabolism and intestinal function
Roth E.; Spittler A.; Oehler R.
Chirurgisches Forschungslabor, Universitatsklinik fur
Chirurgie, Allgemeines Krankenhaus, Wahringer Gurtel
18-20,A-1090 Wien Austria
Wiener Klinische Wochenschrift (Austria)1996,108/21
(669-676)
Glutamine is the most abundant free amino acid of the human
body. In catabolic stress situations such as after operations,
trauma and during sepsis the enhanced transport of glutamine
to splanchnic organs and to blood cells results in an
intracellular depletion of glutamine in skeletal muscle .
Glutamine is an important metabolic substrate for cells
cultivated under in vitro conditions and is a precursor for
purines, pyrimidines and phospholipids. Increasing evidence
suggests that glutamine is a crucial substrate for
immunocompetent cells. Glutamine depletion in the cultivation
medium decreases the mitogen-inducible proliferation of
lymphocytes, possibly by arresting the cells in the Ginf
0-Ginf 1 phase of the cell cycle. Glutamine depletion in
lymphocytes prevents the formation of signals necessary for
late activation. In monocytes glutamine deprivation
downregulates surface antigens responsible for antigen
preservation and phagocytosis. Glutamine is a precursor for
the synthesis of glutathionine and stimulates the formation of
heat-shock proteins. Moreover, there are suggestions that
glutamine plays a crucial role in osmotic regulation of cell
volume and causes phosphorylation of proteins, both of which
may stimulate intracellular protein synthesis. Experimental
studies revealed that glutamine deficiency causes a
necrotising enterocolitis and increases the mortality of
animals subjected to bacterial stress. First clinical studies
have demonstrated a decrease in the incidence of infections
and a shortening of the hospital stay in patients after bone
marrow transplantation by supplementation with glutamine . In
critically ill patients parenteral glutamine reduced nitrogen
loss and caused a reduction of the mortality rate. In surgical
patients glutamine evoked an improvement of several
immunological parameters. Moreover, glutamine exerted a
trophic effect on the intestinal mucosa, decreased the
intestinal permeability and thus may prevent the translocation
of bacteria. In conclusion, glutamine is an important
metabolic substrate of rapidly proliferating cells, influences
the cellular hydration state and has multiple effects on the
immune system, on intestinal function and on protein
metabolism. In several disease states glutamine may
consequently, become an in dispensable nutrient, which should
be provided exogenously during artificial nutrition.
Bioavailability of glutamine and effects of
glutamine on protein metabolism
Darmaun D.
Nemours Children's Clinic, 807 Nira Street,Jacksonville, FL
32207 United States
Nutrition Clinique et Metabolisme (France) 1994, 8/4
(231-240)
Glutamine is synthetized in most tissue and accounts for
two-thirds of the free amino acid pool in skeletal muscle .
Glutamine is not only an interorgan nitrogen shuttle but a
precursor of urinary ammonium, and a favorite fuel of the
immune system and the gut (which uses ~ 17 g of glutamine per
day). Because they were designed at a time when glutamine was
considered both unstable and non-essential, 'traditional'
parenteral nutrition (PN) solutions are devoid of glutamine .
Although 'classic' PN is able to maintain normal rates of
glutamine turnover in healthy subjects or unstressed patients,
classic PN solutions are unable to correct the precipitous
depletion of glutamine pool that accompanies catabolic
illness. Glutamine becomes a 'conditionally essential' amino
acid in these situations. Replenishment of glutamine pool
seems to stimulate protein synthesis, and improves nitrogen
balance in catabolic patients. Supplementation of PN with
glutamine -containing dipeptides or alpha-ketoglutarate (at
doses of 15-50 g/d) is as effective as glutamine itself. The
enteral route represents an attractive alternative for the
supply of glutamine since: 1) glutamine is efficiently
absorbed; 2) nearly 50% of enterally infused glutamine reaches
systemic blood; 3) glutamine residues present in a bound form
in peptides seem to be bioavailable; and 4) in addition to its
protein anabolic effect, glutamine affects intestinal
absorption and trophicity.
The effect of glutamine on the gastrointestinal
tract
Wilmore D.W.
Laboratory for Surgical Metabolism, Brigham and Women's
Hospital, Department of Surgery, 75 Francis Street,Boston, MA
02115 United States
Rivista Italiana di Nutrizione Parenterale ed Enterale
(Italy) 1992, 10/1 (1-6)
Glutamine is an abundant amino acid in the body, but is
absent from most enteral and parenteral formulas. A variety of
studies have demonstrated that catabolic states initiate
breakdown of skeletal-muscle protein and glutamine is formed.
A large proportion of the glutamine is transported to the
gastrointestinal tract and used as a primary fuel source and
incorporated as a substrate in cell synthesis. Administering
glutamine by the enteral or parenteral route enhances
enterocyte proliferation, attenuates atrophy of the pancreas
and prevents hepatic steatosis. Incorporation of glutamine in
nutrient formulations should enhance recovery and function of
the gastrointestinal/tract in our critically ill patients.
Glutamine metabolism by the intestinal tract
Souba W.W.; Smith R.J.; Wilmore D.W.
Department of Surgery, University of Texas Medical School,
Houston, TX 77030 United States
Journal of Parenteral and Enteral Nutrition (United States)
1985, 9/5 (608-617)
Selective metabolism of glutamine by the gut may have
adaptive value. As previously noted, glutamine (and glutamate)
are abundant amino acids that together comprise nearly
one-third of the amino acid nitrogen in meat. Skeletal muscle
proteolysis yields a similar profile of amino acids. The
enzymatic machinery for metabolizing circulating or luminal
glutamine and glutamate in the intestinal epithelium not only
provides energy to the enterocytes, but also may prevent the
delivery of excessive quantities of glutamate into the
systemic circulation where it may have toxic effects. Because
of its anatomical relationship with the liver, it may be
possible for the gut to process glutamine nitrogens in a
unique way. Unlike other tissues which must capture and
transport ammonia by utilizing a carbon carrier, the gut can
harmlessly release this potentially toxic compound into the
portal blood with ammonia trapping mechanisms in the liver
assuring its conversion into urea or back to glutamine . The
increased gut consumption of glutamine in catabolic states may
be related to the ability of this amino acid to displace
glucose as a fuel. During glucocorticoid administration, which
accelerates gut glutamine uptake, the bowel became an organ of
slight glucose release. Thus, glutamine may be preferentially
consumed and oxidized by the gut in place of glucose during
catabolic states. These adaptations may spare glucose for
reparative tissues and inflammatory cells. The concept that
the intestinal tract becomes physiologically quiescent during
illness may merit reconsideration. The data on glutamine
handling by the intestine discussed in this review suggest an
important role for increased intestinal amino acid metabolism
during stress states. The interorgan transfer of glutamine
from muscle to the intestine exemplifies the complex metabolic
cooperation between tissues that is necessary for survival
during a critical illness.
Antagonistic effects of glutamine and histamine on
in vitro lysozyme activity
Krishnamoorthy R.V.; Radha E.
Dept. Zool., Bangalore Univ., Bangalore India
Enzyme 1974, 18/3-4 (253-256)
Glutamine activates and histamine inhibits the activity of
a crystalline lysozyme preparation as well as natural
secretions like tears and nasal mucus.
Calcium
beta-hydroxy-beta-methylbutyrate.1.Potential role as a
phosphate binder in uremia: in vitro study.
Sousa MF; Abumrad NN; Martins C; Nissen S; Riella MC
Department of Medicine, Evangelic School of Medicine,
Curitiba, Brazil.
Nephron (Switzerland) 1996, 72 (3) p391-4
The binding capacity of calcium beta -hydroxy -beta
-methylbutyrate (calcium HMB), compared to other binders, was
investigated in an in vitro study. Fifty milliequivalents of
either calcium HMB, calcium acetate, calcium carbonate,
aluminum hydroxide gel or non-gel aluminum hydroxide was added
to a phosphate solution, titrated (HCl or NaOH), shaken and
centrifuged to four different pH levels at 37 degrees C
(simulating the gastrointestinal milieu). The difference in
phosphate concentration between that of the initial and that
of the supernatant represented from the bound phosphate in the
precipitate. After 4 h at a pH of 6 (representing the
intestinal condition after a meal), the binding percentage
was: calcium acetate = 95.6%, calcium HMB = 92.6%, calcium
carbonate = 46.4%, aluminum hydroxide gel = 33.4% and non-gel
aluminum hydroxide = 17.8%. There was no significant
difference (p > 0.05) between calcium HMB and calcium
acetate. These results suggest that calcium HMB is an
efficient phosphate binder in vitro, which may predict its
effective role in vivo.
Nutritional role of the leucine metabolite beta-
hydroxy beta- methylbutyrate (HMB)
Nissen S.L.; Abumrad N.N.
Dr. S. Nissen, Iowa State University, Ames, IA 50011 United
States
Journal of Nutritional Biochemistry (United States) 1997, 8/6
(300-311)
This review develops the hypothesis that a metabolite of
leucine termed beta -hydroxy beta -methylbutyrate (HMB) plays
a key role in animal metabolism and that in certain
circumstances insufficient amounts of HMB are either consumed
in the diet or produced endogenously to supply tissue needs.
The origin and metabolism of HMB is reviewed including the
role of HMB in cholesterol biosynthesis. HMB feeding studies
in animals are reviewed, which indicate that dietary
supplementation of HMB can improve immune function and health
and can increase the fat content of milk in lactating animals.
Seven human studies are reviewed where HMB wasted. The results
of both animal and human studies indicate that dietary
supplementation of HMB is safe, as evidenced by lack of
physical adverse effects and a lack of effect on blood
hematology and chemistry. The only consistent change in blood
chemistry was a decrease in LDL cholesterol, which changed 7%
(P < .01). In humans undergoing resistance training, HMB
supplementation increased lean mass gains from 50 to 200%,
with similar percentage increases in strength when compared
with unsupplemented subjects. The effects of HMB on muscle
size and function seems to result from a diminution of
exercise-related muscle damage and muscle protein breakdown. A
general hypothesis is proposed that HMB is metabolized to
HMG-CoA in tissues such as muscle, mammary tissue, and certain
immune cells and is used for de novo cholesterol synthesis. In
times of stimulated growth and/or differentiation, HMG-CoA may
be rate-limiting for cholesterol synthesis, which could limit
cell growth or function. It is proposed that feeding HMB can
provide a saturating source of cytosolic HMG-CoA for
cholesterol synthesis and in turn allow for maximal cell
growth and function
|