scholarly journals Extrarenal citrulline disposal in mice with impaired renal function

2014 ◽  
Vol 307 (6) ◽  
pp. F660-F665 ◽  
Author(s):  
Juan C. Marini ◽  
Inka C. Didelija ◽  
Marta L. Fiorotto
Keyword(s):  
Impaired Renal Function ◽  
Radioactive Tracers ◽  
Tissue Protein ◽  
Mean Retention Time ◽  
Main Site ◽  
Plasma Citrulline ◽  
Body Tissues ◽  
Citrulline Synthesis ◽  
Plasma Arginine ◽  
Endogenous Synthesis

The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the “intestinal-renal axis” for arginine synthesis. Although the kidney is the main site for citrulline disposal, it only accounts for ∼60–70% of the citrulline produced. Because the only known fate for citrulline is arginine synthesis and the enzymes that catalyze this reaction are widespread among body tissues, we hypothesized that citrulline can be utilized directly by tissues to meet, at least partially, their arginine needs. To test this hypothesis, we used stable and radioactive tracers in conscious, partially nephrectomized (½ and ⅚) and anesthetized acutely kidney-ligated mouse models. Nephrectomy increased plasma citrulline concentration but did not affect citrulline synthesis rates, thus reducing its clearance. Nephrectomy (⅚) reduced the amount of citrulline accounted for as plasma arginine from 88 to 42%. Acute kidney ligation increased the half-life and mean retention time of citrulline. Whereas the rate of citrulline conversion into plasma arginine was reduced, it was not eliminated. In addition, we observed direct utilization of citrulline for arginine synthesis and further incorporation into tissue protein in kidney-ligated mice. These observations indicate that a fraction of the citrulline produced is utilized directly by multiple tissues to meet their arginine needs and that extrarenal sites contribute to plasma arginine. Furthermore, when the interorgan synthesis of arginine is impaired, these extrarenal sites are able to increase their rate of citrulline utilization.

scholarly journals Glutamine metabolism in chick enterocytes: absence of pyrroline-5-carboxylase synthase and citrulline synthesis

1995 ◽  
Vol 306 (3) ◽  
pp. 717-721 ◽  
Author(s):  
G Wu ◽  
N E Flynn ◽  
W Yan ◽  
D G Barstow
Keyword(s):  
Glutamine Metabolism ◽  
Nutritional Requirement ◽  
Ornithine Carbamoyltransferase ◽  
No Formation ◽  
Weaning Pig ◽  
Citrulline Synthesis ◽  
Metabolic Basis ◽  
Endogenous Synthesis ◽  
Positive Controls ◽  
In Cells

This study was designed to determine whether pyrroline-5-carboxylate (P-5-C) synthase is deficient in chick enterocytes therefore resulting in the lack of synthesis of ornithine and citrulline from glutamine. Post-weaning pig enterocytes, which are known to contain P-5-C synthase and to synthesize both ornithine and citrulline from glutamine, were used as positive controls. Enterocytes were incubated at 37 degrees C for 0-30 min in the presence of 2 mM [U-14C]glutamine or 2 mM ornithine plus 2 mM NH4Cl. In chick enterocytes, glutamine was metabolized to NH3, CO2, glutamate, alanine and aspartate, but not to ornithine, citrulline, arginine or proline. Likewise, there was no formation of citrulline, arginine, alanine or aspartate from ornithine in chick enterocytes. Furthermore, the rate of conversion of ornithine into proline in chick enterocytes was only about 4% of that in cells from pigs. To elucidate the reason for the inability of chick enterocytes to synthesize ornithine and citrulline from glutamine, the activities of the enzymes involved were measured. No activity of P-5-C synthase or ornithine carbamoyltransferase was found in chick enterocytes, in contrast with cells from post-weaning pigs. It was also demonstrated that the activity of ornithine aminotransferase in chick enterocytes was only 3% of that in cells from pigs. Thus the present findings elucidate the biochemical reason for the lack of endogenous synthesis of ornithine and citrulline in chicks. Our results also explain previous observations that ornithine cannot replace arginine or proline in the diet of chicks. We suggest that the absence of P-5-C synthase and ornithine carbamoyltransferase in enterocytes is the metabolic basis for the nutritional requirement of arginine in the chick.

scholarly journals Comparative metabolism of L-methionine, DL-methionine and DL-2-hydroxy 4-methylthiobutanoic acid by broiler chicks

1985 ◽  
Vol 54 (3) ◽  
pp. 621-633 ◽  
Author(s):  
C. Linda Saunderson
Keyword(s):  
Protein Synthesis ◽  
Tissue Distribution ◽  
Broiler Chicks ◽  
Tissue Protein ◽  
Body Tissues ◽  
Comparative Metabolism ◽  
Liver And Kidney

1. Metabolism, in broiler chicks, of DL-2-hydroxy 4-methylthiobutanoic acid (DL-HMB), DL-methionine and L-methionine was compared in vivo using 14C-labelled tracers.2. The distribution of L-[1-14C]methionine and DL-[1-14C]HMB in the major body tissues was examined for a period of 120 min after administration.3. The relative oxidation (14CO2, exhaled), excretion and incorporation into tissue protein of L-[l-14C]methionine, DL-[l-14C]methionine and DL-[1-14C]HMB were measured in fed birds.4. Tissue distribution of L-[1-14C]methionine and DL-[1-14C]HMB differed during 60–90 min following administration.5. The production of 14CO2, from each of the tracers was similar but excretion of 14C-labelled material was very different with the greatest excretion from DL-[1-14C]HMB and the least from L[1-14C]methionine.6. The incorporation of 14C into tissue proteins varied with the tracer given and the tissue examined. Liver and kidney had equivalent incorporation from each of the tracers while other tissues examined showed lower incorporation from DL-[1-14C]methionine and DL-[1-14C]HMB.7. The results show that DL-HMB, D-methionine and L-methionine are metabolized differently in vivo and that they are excreted in differing proportions. There is also a difference in the ability of each to act as a precursor for protein synthesis in tissues other than liver.

scholarly journals De novo synthesis is the main source of ornithine for citrulline production in neonatal pigs

2012 ◽  
Vol 303 (11) ◽  
pp. E1348-E1353 ◽  
Author(s):  
Juan C. Marini ◽  
Barbara Stoll ◽  
Inka Cajo Didelija ◽  
Douglas G. Burrin
Keyword(s):  
Amino Acid ◽  
De Novo ◽  
Neonatal Period ◽  
De Novo Synthesis ◽  
Physiological Factors ◽  
Neonatal Piglets ◽  
Neonatal Pigs ◽  
Citrulline Synthesis ◽  
Plasma Arginine ◽  
Infusion Protocol

Citrulline is an amino acid synthesized in the gut and utilized for the synthesis of the conditionally essential amino acid arginine. Recently, the origin of the ornithine utilized for citrulline synthesis has become a matter of discussion. Multiple physiological factors may have contributed to the differences found among different researchers; one of these is the developmental stage of the subjects studied. To test the hypothesis that during the neonatal period de novo synthesis is the main source of ornithine for citrulline synthesis, neonatal piglets were infused intravenously or intragastrically with [U-13C6]arginine, [U-13C5]glutamine, or [U-13C5]proline during the fasted and fed periods. [ ureido-15N]citrulline and [2H2]ornithine were infused intravenously for the entire infusion protocol. During fasting, plasma proline (13%) and ornithine (19%) were the main precursors for citrulline synthesis, whereas plasma arginine (62%) was the main precursor for plasma ornithine. During feeding, enteral (27%) and plasma (12%) proline were the main precursors for the ornithine utilized in the synthesis of citrulline, together with plasma ornithine (27%). Enteral proline and glutamine were utilized directly by the gut to produce ornithine utilized for citrulline synthesis. Arginine was not utilized by the gut, which is consistent with the lack of arginase activity in the neonate. Arginine, however, was the main source (47%) of plasma ornithine and in this way contributed to citrulline synthesis. In conclusion, during the neonatal period, the de novo pathway is the predominant source for the ornithine utilized in the synthesis of citrulline, and proline is the preferred precursor.

scholarly journals Incorporating turnover in estimates of protein retention efficiency for different body tissues

2006 ◽  
Vol 95 (2) ◽  
pp. 246-254 ◽  
Author(s):  
C. Z. Roux
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Whole Body ◽  
Muscle Fibres ◽  
Retention Efficiency ◽  
Tissue Protein ◽  
Protein Retention ◽  
Body Tissues ◽  
Breakdown Rates ◽  
The Relationship

Formulated in terms of protein synthesis (PS) and protein retention (PR), a definition of turnover-related protein retention efficiency (kP) allows the expression kP=[1+(PS/PR)/6]−1, 6 representing the ratio of the energy equivalent of protein to the cost of synthesis. By combining plausible hormonal and cellular control mechanisms of protein (P) growth, it is possible to derive (PS/PR)=[Q{(P/α)−(4/9)Y−1}]−1+1, allowing the calculation of kPby substitution. The symbol α represents the limit value of protein growth, while the term 4/9 derives from the power in the relationship between the concentration of growth factor-related activator in the nucleus and cell volume (cv). Y is the power in the relationship between cv and total tissue protein, and Q represents the proportion of growth factor-activated nuclei in a tissue. The proportion Q can be estimated from simple functions of intake rates or blood growth factor concentrations. Estimates of Y are derived from histological considerations or calculated from experimental observations; Y=1 for multinucleated skeletal muscle fibres and Y=1/3, 1/2, 1/6 on average for mononucleated cell tissues, skin or bone and viscera, respectively. To apply kPto the whole body, an average value of Y=1/2 can be taken. Experimental observations on tissue protein synthesis and breakdown rates yield direct estimates of kPin satisfactory agreement with comparable theoretical predictions.

Manipulation of citrulline availability in humans

2007 ◽  
Vol 293 (5) ◽  
pp. G1061-G1067 ◽  
Author(s):  
Carole Rougé ◽  
Clotilde Des Robert ◽  
Alexander Robins ◽  
Olivier Le Bacquer ◽  
Christelle Volteau ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Balance ◽  
Nitrogen Excretion ◽  
Gas Chromatography Mass Spectrometry ◽  
Urea Nitrogen ◽  
Plasma Citrulline ◽  
Plasma Arginine ◽  
Trapping Agent ◽  
Arginine Level

To determine whether circulating citrulline can be manipulated in vivo in humans, and, if so, whether citrulline availability affects the levels of related amino acids, nitric oxide, urinary citrulline, and urea nitrogen, 10 healthy volunteers were studied on 3 separate days: 1) under baseline conditions; 2) after a 24-h treatment with phenylbutyrate (0.36 g·kg−1·day−1), a glutamine “trapping” agent; and 3) during oral l-citrulline supplementation (0.18 g·kg−1·day−1), in randomized order. Plasma, erythrocyte (RBC), and urinary citrulline concentrations were determined by gas chromatography-mass spectrometry at 3-h intervals between 1100 and 2000 on each study day. Regardless of treatment, RBC citrulline was lower than plasma citrulline, with an RBC-to-plasma ratio of 0.60 ± 0.04, and urinary citrulline excretion accounted for <1% of the citrulline load filtered by kidney. Phenylbutyrate induced an ∼7% drop in plasma glutamine ( P = 0.013), and 18 ± 14% ( P < 0.0001) and 19 ± 17% ( P < 0.01) declines in plasma and urine citrulline, respectively, with no alteration in RBC citrulline. Oral l-citrulline administration was associated with 1) a rise in plasma, urine, and RBC citrulline (39 ± 4 vs. 225 ± 44 μmol/l, 0.9 ± 0.3 vs. 6.2 ± 3.8 μmol/mmol creatinine, and 23 ± 1 vs. 52 ± 9 μmol/l, respectively); and 2) a doubling in plasma arginine level, without altering blood urea or urinary urea nitrogen excretion, and thus enhanced nitrogen balance. We conclude that 1) depletion of glutamine, the main precursor of citrulline, depletes plasma citrulline; 2) oral citrulline can be used to enhance systemic citrulline and arginine availability, because citrulline is bioavailable and very little citrulline is lost in urine; and 3) further studies are warranted to determine the mechanisms by which citrulline may enhance nitrogen balance in vivo in humans.

scholarly journals Occurrence of ornithine decarboxylase and polyamines in cartilage

1977 ◽  
Vol 162 (2) ◽  
pp. 347-350 ◽  
Author(s):  
P D Conroy ◽  
D M Simms ◽  
J J Pointon
Keyword(s):  
Chick Embryo ◽  
Ornithine Decarboxylase ◽  
Costal Cartilage ◽  
Decarboxylase Activity ◽  
Ph Optimum ◽  
Tissue Protein ◽  
Ornithine Decarboxylase Activity ◽  
Body Tissues ◽  
Human Foetuses

The activity of ornithine decarboxylase was investigated in cartilage from chick embryos, rabbits, rats and human foetuses. The enzyme activity in these cartilages was of the same order as the detected in other body tissues. Ornithine decarboxylase activity in chick-embryo cartilage and liver was the same when compared on the basis of total soluble tissue protein. The cartilage enzyme exhibited a pH optimum of 6.5 and a Km for ornithine of 0.16mM. Ornithine decarboxylase activity in chick-embryo pelvic leaflets was maintained at the value in vivo for up to 22h when the isolated tissue was incubated in a modified Waymouth's medium (MB 752/1) at 37 degrees C. After addition of cycloheximide to the incubation medium, ornithine decarboxylase activity declined, with a half-life of 40 min. The concentrations of the polyamines spermidine and spermine in chick-embryo pelvic cartilage and rabbit costal cartilage were of the same order as the concentrations detected in other tissues.

The Metabolism of Tartrate in Man and the Rat

1978 ◽  
Vol 54 (3) ◽  
pp. 273-281
Author(s):  
V. S. Chadwick ◽  
A. Vince ◽  
M. Killingley ◽  
O. M. Wrong
Keyword(s):  
Carbon Dioxide ◽  
Urinary Excretion ◽  
Direct Injection ◽  
Intestinal Bacteria ◽  
The Body ◽  
Sodium Tartrate ◽  
Main Site ◽  
Body Tissues ◽  
System L ◽  
The Difference

1. Sodium tartrate labelled with 14C was given orally and parenterally to man and rats, and by direct injection into the caecum in rats. From the differences in urinary excretion after oral and parenteral administration intestinal absorption of tartrate was calculated as 18% of the dose in man and 81% in rats. Urinary tartrate was equivalent to 14% of the dose in man and 70% in rats, the difference between absorption and urinary excretion representing metabolism in body tissues. 2. Both man and the rat excreted part of the 14C as respiratory carbon dioxide. This occurred to a small extent after parenteral injection, suggesting metabolism of tartrate by body tissues, but was greater after oral or intracaecal administration, indicating that the main site of tartrate metabolism is the intestine. 3. Several genera of intestinal bacteria were shown to liberate [14C]carbon dioxide from labelled tartrate, and in a faecal incubation system l-tartrate, the natural isomer, was metabolized five times as rapidly as d-tartrate. 4. Oral sodium l-tartrate, 1·5 mmol day—1 kg—1, was given to two subjects and was shown to alkalinize the urine like sodium salts of other organic acids which are metabolized in the body. The reduction in renal hydrogen ion excretion showed that an average of 84% of the dose was metabolized. 5. Only 5% of labelled tartrate given by mouth appeared in faeces, and pharmacological doses of unlabelled l-tartrate had little or no aperient effect. 6. No evidence of toxicity of l-tartrate was encountered.

Anatomy and physiology of the gastrointestinal tract of the Julia Creek dunnart, Sminthopsis douglasi (Marsupialia : Dasyuridae)

2000 ◽  
Vol 48 (5) ◽  
pp. 475 ◽  
Author(s):  
I. D. Hume ◽  
C. Smith ◽  
P. A. Woolley
Keyword(s):  
Gastrointestinal Tract ◽  
Cell Walls ◽  
Plant Cell Walls ◽  
Mean Retention Time ◽  
Main Site ◽  
Anatomy And Physiology ◽  
Well Differentiated ◽  
Minced Meat ◽  
Mealworm Larvae ◽  
Passage Times

The gastrointestinal tract of the endangered Julia Creek dunnart (Sminthopsis douglasi), the largest member of the genus Sminthopsis, consists of a simple, unilocular stomach and an intestine of relatively uniform calibre throughout. There is no hindgut caecum, in common with other Australian carnivorous marsupials. Brunner’s glands form a collar at the proximal end of the duodenum; they consist of simple uncoiled tubes at Day 45 of pouch life but are well differentiated at Day 60, before the young take their first solid food at Day 65–70. Rate of passage of digesta was measured in nine adult Julia Creek dunnarts on diets of minced meat with either mealworm larvae or adult crickets added, using pulse doses of the solute marker Co–EDTA and large (0.5–1.0 mm) particles of plant cell walls mordanted with Cr. Transit time (time of first appearance in the faeces) of both markers (P < 0.001) and mean retention time (the average time markers are retained in the tract) of the solute marker (P < 0.05) were shorter on the diet containing mealworms than the cricket diet. These results suggest that emptying of the stomach (the main site of digesta retention in carnivores) was delayed on the cricket diet, possibly because of longer digestion times as a result of a tougher exoskeleton. Comparison with other data suggests that total tract passage times increase among dasyurids as body size increases.

Cold Promoted Activation of Factor VII VI. Effect of Inhibitors

1973 ◽  
Vol 29 (03) ◽  
pp. 633-643
Author(s):  
H Gjønnæss
Keyword(s):  
Soya Bean ◽  
Factor Vii ◽  
Plasma Kallikrein ◽  
Contact Activation ◽  
Activation Reaction ◽  
Hexadimethrine Bromide ◽  
Bean Trypsin Inhibitor ◽  
Plasma Arginine ◽  
Kallikrein Activity ◽  
Effect Of Inhibitors

SummaryThe cold promoted activation of factor VII occurs in parallel with an activation of a plasma arginine esterase, and, on inhibition of the cold activation of factor VII, the esterase activation also decreased. The inhibitor pattern supported our theory that the arginine esterase that is activated in the cold activation of factor VII is plasma kallikrein.The cold activation of factor VII was completely inhibited with soya bean trypsin inhibitor in doses that did not interfere with the contact activation. On the other hand, inhibition of the contact activation with hexadimethrine bromide did not interfere with the cold activation of factor VII except when this was kaolin induced. Contact and cold activation therefore appear to represent two different pathways for the activation of factor VII. The cold activation reaction is probably mediated by the activation of plasma prekallikrein, and inhibition of the plasma kallikrein activity correlates with the inhibition of the cold promoted activation of factor VII.

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