Nitrogen Homoeostasis in man: Influence of Protein Intake on the Amplitude of Diurnal Cycling of Body Nitrogen

1994 ◽  
Vol 86 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Gill M. Price ◽  
David Halliday ◽  
Paul J. Pacy ◽  
Marcelo R. Quevedo ◽  
D. Joe Millward
Keyword(s):  
Amino Acid ◽  
Protein Intake ◽  
The Body ◽  
N Balance ◽  
N Losses ◽  
Body Protein ◽  
Fed State ◽  
Excretion Rates ◽  
Amino Acid Balance ◽  
Diurnal Cycling

1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed increasing protein intakes. N balance was estimated during a 48 h period of consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of adaptation to diets containing 0.36 +0.01, 0.77 + 0.03, 1.59 +0.08 and 2.31 +0.65 g of protein day−1 kg−1. N losses were determined from measured urinary N excretion corrected for changes in the body urea pool, and estimated faecal and miscellaneous losses. [13C] Leucine and [2H5]phenylalanine balances were measured during a primed, continuous infusion of the two amino acids during the fasting and feeding phase on the second day. 2. Increasing fasting N losses were observed (47 +7, 60+6, 95+15 and 140+36 mg day−1 kg−1) on the four intakes, with corresponding increasing fed gains of 8.2+3.9, 40.2+7.1, 112+24 and 180+ 56 mg day−1 kg−1. 3. Increasing fed-state amino acid gains with increasing protein intake were observed with both [13C]leucine and [2H5]phenylalanine, whereas increasing fasting amino acid losses were confirmed with [13C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly in the range of 10–50% lower than expected from the N excretion rates. This may reflect the timing of the amino acid balance measurements and non-uniform rates of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of both N and amino acid balances that the amplitude of the diurnal cycling of body protein N in human adults increases with increasing dietary protein intake. Thus one component of the protein requirement for N balance reflects a demand for repletion of fasting losses which increases with increasing habitual protein intake.

Whole-body leucine and lysine metabolism: response to dietary protein intake in young men

1981 ◽  
Vol 240 (6) ◽  
pp. E712-E721 ◽  
Author(s):  
K. J. Motil ◽  
D. E. Matthews ◽  
D. M. Bier ◽  
J. F. Burke ◽  
H. N. Munro ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dietary Protein ◽  
Protein Intake ◽  
Whole Body ◽  
Dietary Protein Intake ◽  
Body Protein ◽  
Fed State ◽  
Amino Acid Requirements ◽  
Maintenance Requirements ◽  
Lysine Metabolism

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1–13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.

Nitrogen Homoeostasis in man: The Diurnal Responses of Protein Synthesis and Degradation and Amino Acid Oxidation to Diets with Increasing Protein Intakes

1994 ◽  
Vol 86 (1) ◽  
pp. 103-118 ◽  
Author(s):  
Paul J. Pacy ◽  
Gill M. Price ◽  
David Halliday ◽  
Marcello R. Quevedo ◽  
D. Joe Millward
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Whole Body ◽  
Body Protein ◽  
Fed State ◽  
Leucine Kinetics ◽  
Synthesis And Degradation

1. The diurnal changes in whole body protein turnover associated with the increasing fasting body nitrogen (N) losses and feeding gains with increasing protein intake were investigated in normal adults. [13C]Leucine, [2H5]phenylalanine and [2H2]tyrosine kinetics, were measured during an 8h primed, continuous infusion during the fasting and feeding phase together with fed-state N turnover assessed with [15N]glycine after 12 days of adaptation to diets containing 0.36 (LP), 0.77 (MP), 1.59 (GP) and 2.07 (HP) g of protein day−1 kg−1. Measurements were also made of fasting and fed resting metabolic rate and plasma hormone levels. 2. Resting metabolic rate in the fasted and fed state was not influenced by dietary protein intake, but was increased by feeding (11-13%, P <0.01) with no influence of dietary protein concentration. Fasting plasma insulin levels were not influenced by protein intake and were increased by feeding independent of protein intake. Fasted but not fed values of insulinlike growth factor-1 increased with protein intake, although no feeding response was observed. Thyroid hormones (free and total tri-iodothyronine) did not change in any state. 3. For leucine with increasing protein intake the increasing fasting losses reflected increasing rates of protein degradation, although the changes were small and only significant between GP and MP intakes. The increasing leucine gain on feeding was associated with increasing rates of protein synthesis and falling rates of protein degradation, reflecting a progressive inhibition of degradation with feeding, and a change from inhibition of synthesis (LP diet) to stimulation (GP and HP diets). Mean daily rates of synthesis and degradation did not change with protein intake. 4. Phenylalanine and tyrosine kinetics were calculated from adjusted values based on leucine kinetics and published data of the hepatic/plasma enrichment ratio. With the increased protein intake, the increasing fasting losses of phenylalanine (GP > MP) were mediated by increasing rates of degradation (paired t-tests). The increasing phenylalanine gain (GP > MP > LP) was due to increasing fed-state rates of synthesis and falling rates of degradation, reflecting a progressive inhibition of degradation, a stimulation of hydroxylation and a variable response of synthesis ranging from inhibition at the lowest intake to stimulation at higher intakes. For tyrosine a similar progressive inhibition of degradation with intake was shown. Mean daily rates of synthesis and degradation (phenylalanine) and degradation (tyrosine) did not change with protein intake. 5. Estimation of protein turnover from 15N excretion in urea and ammonia during 9 h after 1 h intravenous infusion of [15N]glycine in the fed state on the LP, MP and GP diets indicated that neither synthesis nor degradation were influenced by dietary protein level. Synthesis estimated from 15N kinetics was significantly correlated with that determined from leucine kinetics (r = 0.78, n = 14, P <0.01) and from phenylalanine kinetics (r = 0.53, n = 14, P <0.05), and degradation estimated from 15N kinetics was significantly correlated with that determined from leucine kinetics (r = 0.60, n = 14, P <0.05). Thus the [15N]glycine, [13C]leucine and [2H5]phenylalanine methods gave broadly comparable results. 6. We conclude that the feeding response of protein synthesis, degradation and amino acid oxidation reflects the combined impact of insulin and tissue amino acid levels with insulin inhibiting degradation and with amino acids both stimulating synthesis and oxidation and also further inhibiting degradation. Although the dietary protein level influences the extent of these feeding responses, it does not influence the mean daily rate of protein turnover. The rate of whole body protein turnover per se is unlikely to provide an indicator of protein nutritional status.

scholarly journals Impact of habituated dietary protein intake on fasting and postprandial whole-body protein turnover and splanchnic amino acid metabolism in elderly men: a randomized, controlled, crossover trial

2020 ◽  
Vol 112 (6) ◽  
pp. 1468-1484 ◽  
Author(s):  
Grith Højfeldt ◽  
Jacob Bülow ◽  
Jakob Agergaard ◽  
Ali Asmar ◽  
Peter Schjerling ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Turnover ◽  
Protein Intake ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
High Protein ◽  
Whole Body ◽  
Body Protein ◽  
Protein Absorption ◽  
Fasted State

ABSTRACT Background Efficacy of protein absorption and subsequent amino acid utilization may be reduced in the elderly. Higher protein intakes have been suggested to counteract this. Objectives We aimed to elucidate how habituated amounts of protein intake affect the fasted state of, and the stimulatory effect of a protein-rich meal on, protein absorption, whole-body protein turnover, and splanchnic amino acid metabolism. Methods Twelve men (65–70 y) were included in a double-blinded crossover intervention study, consisting of a 20-d habituation period to a protein intake at the RDA or a high amount [1.1 g · kg lean body mass (LBM)−1 · d−1 or &gt;2.1 g · kg LBM−1 · d−1, respectively], each followed by an experimental trial with a primed, constant infusion of D8-phenylalanine and D2-tyrosine. Arterial and hepatic venous blood samples were obtained after an overnight fast and repeatedly 4 h after a standardized meal including intrinsically labeled whey protein concentrate and calcium-caseinate proteins. Blood was analyzed for amino acid concentrations and phenylalanine and tyrosine tracer enrichments from which whole-body and splanchnic amino acid and protein kinetics were calculated. Results High (compared with the recommended amount of) protein intake resulted in a higher fasting whole-body protein turnover with a resultant mean ± SEM 0.03 ± 0.01 μmol · kg LBM−1 · min−1 lower net balance (P &lt; 0.05), which was not rescued by the intake of a protein-dense meal. The mean ± SEM plasma protein fractional synthesis rate was 0.13 ± 0.06%/h lower (P &lt; 0.05) after habituation to high protein. Furthermore, higher fasting and postprandial amino acid removal were observed after habituation to high protein, yielding higher urea excretion and increased phenylalanine oxidation rates (P &lt; 0.01). Conclusions Three weeks of habituation to high protein intake (&gt;2.1 g protein · kg LBM−1 · d−1) led to a significantly higher net protein loss in the fasted state. This was not compensated for in the 4-h postprandial period after intake of a meal high in protein. This trial was registered at clinicaltrials.gov as NCT02587156.

Influence of protein intake on whole body and splanchnic leucine kinetics in humans

1997 ◽  
Vol 272 (4) ◽  
pp. E584-E591 ◽  
Author(s):  
M. Cayol ◽  
Y. Boirie ◽  
F. Rambourdin ◽  
J. Prugnaud ◽  
P. Gachon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Intake ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Body ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Protein X ◽  
Pool Model

The influence of the protein content of the meal on protein turnover was investigated in the splanchnic bed and in the remaining parts of the body in humans. Two groups of five subjects consumed every 20 min a liquid formula providing either 1.5 g protein x kg(-1) x day(-1) (P) or no protein (PF). L-[1-(13)C]leucine and L-[5,5,5-(2)H3]leucine were administered by vein and gut, respectively. An open two-pool model was developed to calculate leucine kinetics in both compartments, with the assumption that the enrichment of the tracers incorporated into very low density lipoprotein apolipoprotein B100 at isotopic steady state could reflect the leucine labeling in the splanchnic region. Nonsplanchnic uptake and release of leucine were not significantly different in the two groups. Within the splanchnic area, leucine uptake was 2.1 times higher in the P than in the PF group (P < 0.01), whereas leucine release was reduced but not significantly (-19%) in the P group compared with the PF group. Moreover, data derived from this model showed that protein intake induced an increase in whole body protein synthesis and no change in whole body protein breakdown. Albumin synthesis, as well as its contribution to whole body protein synthesis, was significantly enhanced by protein intake.

scholarly journals TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY

1943 ◽  
Vol 77 (3) ◽  
pp. 277-295 ◽  
Author(s):  
S. C. Madden ◽  
J. R. Carter ◽  
A. A. Kattus ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Intake ◽  
Protein Production ◽  
The Body ◽  
Acid Mixture ◽  
Negative Nitrogen Balance ◽  
Growth Mixture

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.

scholarly journals The mysteries of nitrogen balance

1999 ◽  
Vol 12 (1) ◽  
pp. 25-54 ◽  
Author(s):  
J. C Waterlow
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Urea Cycle ◽  
N Balance ◽  
Single Amino Acid ◽  
Whole Body ◽  
Acid Oxidation ◽  
Physiological Level ◽  
Body Protein ◽  
Urea Production

AbstractThe first part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the first enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all five urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH3, that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are influenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to fill this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

8 Functional Role of Histidine in Diets of Young Pigs

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 13-13
Author(s):  
Jaap van Milgen ◽  
Nathalie Le Floc’h
Keyword(s):  
Amino Acid ◽  
Dose Response ◽  
The Body ◽  
Whole Body ◽  
Body Protein ◽  
Constituent Amino Acid ◽  
Young Pigs ◽  
Hydrolysis Of ◽  
The Brain

Abstract Histidine is a constituent amino acid of body proteins and, once incorporated in protein, histidine can be methylated post-translationally to methyl-histidine. Histidine is also a precursor of histamine, a neurotransmitter and involved in the immune response. Histidine and histamine are constituents of a number of dipeptides, which act as pH buffers, metal chelating agents, and anti-oxidants, especially in skeletal muscles and in the brain. A considerable fraction of whole-body histidine is present as carnosine, the dipeptide of histidine and β-alanine. In the longissimus muscle, about 40% of the total histidine content is present as carnosine. The histidine in carnosine can be methylated to anserine or balenine, and the pig is among the few species that synthesize both forms. Hydrolysis of body protein and of histidine-containing dipeptides results in the release of the constituent amino acids. However, only the histidine of protein and carnosine can be reused for protein synthesis. Methyl-histidine is either excreted in the urine or remains bound in the dipeptides and accumulates in the body. Because carnosine represents such a large histidine reservoir, a dietary histidine deficiency may not directly lead to a reduction in growth, especially if growth is given a higher priority for histidine utilization than maintaining or depleting the histidine-containing dipeptide reserves. Few histidine dose-response studies have been done in piglets and differences in the estimated requirements may be due to differences in diluting or depleting the dipeptide reserves. However, at low histidine intakes, both feed intake and growth are reduced and a reduction of the histidine-to-lysine supply by 1 percentage point results in a growth reduction of 4%. Histidine dose-response studies need to consider the role of histidine as a constituent amino acid of body protein as well as its role in dipeptides.

scholarly journals Assessing the whole-body protein synthetic response to feeding in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Luc J. C. van Loon
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Intake ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein ◽  
Breakdown Rates

All tissues are in a constant state of turnover, with a tightly controlled regulation of protein synthesis and breakdown rates. Due to the relative ease of sampling skeletal muscle tissue, basal muscle protein synthesis rates and the protein synthetic responses to various anabolic stimuli have been well defined in human subjects. In contrast, only limited data are available on tissue protein synthesis rates in other organs. Several organs such as the brain, liver and pancreas, show substantially higher (basal) protein synthesis rates when compared to skeletal muscle tissue. Such data suggest that these tissues may also possess a high level of plasticity. It remains to be determined whether protein synthesis rates in these tissues can be modulated by external stimuli. Whole-body protein synthesis rates are highly responsive to protein intake. As the contribution of muscle protein synthesis rates to whole-body protein synthesis rates is relatively small considering the large amount of muscle mass, this suggests that other organ tissues may also be responsive to (protein) feeding. Whole-body protein synthesis rates in the fasted or fed state can be quantified by measuring plasma amino acid kinetics, although this requires the production of intrinsically labelled protein. Protein intake requirements to maximise whole-body protein synthesis may also be determined by the indicator amino acid oxidation technique, but the technique does not allow the assessment of actual protein synthesis and breakdown rates. Both approaches have several other methodological and inferential limitations that will be discussed in detail in this paper.

Leucine and protein metabolism in the lactating dairy cow mammary gland: responses to supplemental dietary crude protein intake

1996 ◽  
Vol 63 (2) ◽  
pp. 209-222 ◽  
Author(s):  
Brian J. Bequette ◽  
John A. Metcalf ◽  
Diane Wray-Cahen ◽  
F. R. Colette Backwell ◽  
John D. Sutton ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Amino Acid ◽  
Protein Metabolism ◽  
Protein Intake ◽  
Crude Protein ◽  
Milk Protein ◽  
Protein Supplementation ◽  
Whole Body ◽  
Body Protein

SummaryMammary gland protein metabolism, determined by an arteriovenous difference technique, was monitored in four Holstein-Friesian dairy cows in response to supplemental dietary protein (provided as rumen-protected soyabean meal) during late lactation (weeks 24–30). Each cow was offered two isoenergetic diets composed of grass silage (170 g crude protein/kg dry matter) plus either a low (108 g/kg) or medium (151 g/kg) crude protein concentrate in a single crossover design involving two 21 d periods. On day 21, arteriovenous measurements across the mammary gland were made during a 13 h continuous i.v. infusion of [1-13C]leucine and with frequent (2 hourly) milk sampling during the final 6 h. Although total milk yield was slightly increased (+1 kg/d) by protein supplementation, milk protein yield was not significantly affected. Whole body protein flux (protein synthesis plus oxidation) was not significantly affected by supplementation. Total mammary gland protein synthesis (milk plus non-milk protein) was also not affected by supplementation but on both diets gland synthesis was always greater (by 20–59%) than milk protein output. The fractional oxidation rate of leucine by the mammary gland was significantly increased by protein supplementation (0·047 v. 0·136). Although the enrichment of leucine in secreted milk protein continued to increase, the final value (at 13 h) was 0·94 of the arterial plasma free leucine plateau value (not significantly different), suggesting almost exclusive use of plasma free leucine for milk protein synthesis. Based on current feeding schemes for dairy cattle, a fixed proportion (0·65–0·75) of the additional protein intake (+490 g/d) should have been partitioned into milk protein. Instead, leucine oxidation by the mammary gland was increased. Whether oxidation of other amino acids was also enhanced is unknown but if amino acid oxidation and the ‘additional’ non-milk protein synthesis occurring in the gland are not crucial to milk synthesis, then by reducing such activities improvements in the efficiency of converting absorbed amino acid into milk protein can be achieved.

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