Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.

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Impairment of albumin and whole body postprandial protein synthesis in compensated liver cirrhosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00333.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. E304-E311 ◽

Cited By ~ 22

Author(s):

P. Tessari ◽

R. Barazzoni ◽

E. Kiwanuka ◽

G. Davanzo ◽

G. De Pergola ◽

...

Keyword(s):

Protein Synthesis ◽

Liver Cirrhosis ◽

Disease Stage ◽

Whole Body ◽

Synthesis Rate ◽

Albumin Concentration ◽

Mixed Meal ◽

Body Protein ◽

Control Subjects ◽

Class B

To investigate the anabolic effects of feeding in cirrhosis, we measured albumin fractional synthesis rate (FSR) and whole body protein synthesis in six nondiabetic patients with stable liver cirrhosis (three in the Child-Pugh classification Class A, three in Class B) and in seven normal control subjects, before and after administration of a 4-h mixed meal. Leucine tracer precursor-product relationships and whole body kinetics were employed at steady state. Basal levels of postabsorptive albumin concentration and FSR, whole body leucine rate of appearance, oxidation, and nonoxidative leucine disposal (NOLD, ≈protein synthesis) were similar in the two groups. However, after the meal, in the patients neither albumin FSR (from 8.5 ± 1.5 to 8.8 ± 1.8 %/day) nor NOLD (from 1.69 ± 0.22 to 1.55 ± 0.26 μmol · kg−1· min−1) changed ( P = nonsignificant vs. basal), whereas they increased in control subjects (albumin FSR: from 10.9 ± 1.5 to 15.9 ± 1.9 %/day, P < 0.002; NOLD: from 1.80 ± 0.14 to 2.10 ± 0.19 μmol · kg−1· min−1, P = 0.032). Thus mixed meal ingestion did not stimulate either albumin FSR or whole body protein synthesis in compensated liver cirrhosis. The mechanism(s) maintaining normoalbuminemia at this disease stage need to be further investigated.

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Whole Body Protein Metabolism in Human Pulmonary Tuberculosis and Undernutrition: Evidence for Anabolic Block in Tuberculosis

Clinical Science ◽

10.1042/cs0940321 ◽

1998 ◽

Vol 94 (3) ◽

pp. 321-331 ◽

Cited By ~ 58

Author(s):

Derek C. MacAllan ◽

Margaret A. McNurlan ◽

Anura V. Kurpad ◽

George De Souza ◽

Prakash S. Shetty ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Body Mass ◽

Protein Metabolism ◽

Protein Turnover ◽

Nutrition Support ◽

Whole Body ◽

Body Protein ◽

Leucine Kinetics ◽

Body Energy ◽

Net Protein

1. Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection. 2. We investigated whole body energy and protein metabolism in nine subjects with pulmonary tuberculosis, six undernourished subjects (body mass index < 18.5 kg/m2) and seven control subjects from an Indian population. Fasting subjects were infused with l-[1-13C] leucine (2.3 μmol · h−1 · kg−1) for 8 h, 4 h fasted then 4 h fed. Leucine kinetics were derived from 13C-enrichment of leucine and α-ketoisocaproic acid in plasma and CO2 in breath. 3. Undernourished subjects, but not tuberculosis subjects, had higher rates of whole body protein turnover per unit lean body mass than controls [163.1 ± 9.4 and 148.6 ± 14.6 μmol compared with 142.8 ± 14.7 μmol leucine/h per kg, based on α-ketoisocaproic acid enrichment (P = 0.039)]. 4. In response to feeding, protein oxidation increased in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0 ± 10.5 compared with 37.1 ± 5.4 μmol · h−1 · kg−1 in controls), resulting in a less positive net protein balance in the fed phase (controls, 39.7 ± 6.2; undernourished subjects, 29.2 ± 10.6; tuberculosis subjects, 24.5 ± 93; P = 0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of leucine flux (33.2%) than either of the other groups (controls, 24.0%; undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase fasting whole body protein turnover but impaired the anabolic response to feeding compared with control and undernourished subjects. Such ‘anabolic block’ may contribute to wasting in tuberculosis and may represent the mechanism by which some inflammatory states remain refractory to nutrition support.

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Chloroquine reduces whole body proteolysis in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.1.e183 ◽

1994 ◽

Vol 267 (1) ◽

pp. E183-E186 ◽

Cited By ~ 2

Author(s):

P. De Feo ◽

E. Volpi ◽

P. Lucidi ◽

G. Cruciani ◽

F. Santeusanio ◽

...

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Plasma Concentrations ◽

Whole Body ◽

Body Protein ◽

Leucine Kinetics ◽

Lysosomal Proteolysis ◽

Therapeutic Doses

The antimalaric drug chloroquine is a well known inhibitor of lysosomal proteolysis in vitro. The present study tests the hypothesis that therapeutic doses of the drug decrease proteolysis also in vivo in humans. Leucine kinetics were determined in 20 healthy volunteers given 12 and 1.5 h before the studies 250 and 500 mg, respectively, of chloroquine phosphate (n = 10) or similar tablets of placebo (n = 10). Chloroquine reduced the rates of leucine appearance, a measure of whole body proteolysis, from 2.45 +/- 0.08 to 2.19 +/- 0.08 mumol.kg-1.min-1 (P = 0.038) and those of nonoxidative leucine disposal, an estimate of whole body protein synthesis, from 2.16 +/- 0.08 to 1.95 +/- 0.06 mumol.kg-1.min-1 (P = 0.050). The drug resulted also in a marginally significant (P = 0.051) decrement in the plasma concentrations of glucose. The effects of chloroquine on protein turnover might be potentially useful in counteracting protein wasting complicating several catabolic diseases, whereas those on glucose metabolism can explain the sporadic occurrence of severe hypoglycemic episodes in malaria patients chronically treated with this drug.

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Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00050.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. E639-E646 ◽

Cited By ~ 7

Author(s):

Michael J. Toth ◽

Cynthia K. Sites ◽

Dwight E. Matthews

Keyword(s):

Postmenopausal Women ◽

Protein Metabolism ◽

Protein Turnover ◽

Hormone Replacement ◽

Menopausal Status ◽

Ovarian Hormones ◽

Hormone Deficiency ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [13C]leucine in healthy premenopausal ( n = 15, 49 ± 1 yr) and postmenopausal ( n = 18, 53 ± 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [13C]leucine and [2H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo ( n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.

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Leucine kinetics in endurance-trained humans

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.1.1 ◽

1990 ◽

Vol 69 (1) ◽

pp. 1-6 ◽

Cited By ~ 28

Author(s):

L. S. Lamont ◽

D. G. Patel ◽

S. C. Kalhan

Keyword(s):

Energy Expenditure ◽

Protein Turnover ◽

Resting Energy Expenditure ◽

Whole Body ◽

Body Protein ◽

Energy Expenditures ◽

Leucine Kinetics ◽

Constant Rate ◽

Tracer Dilution ◽

Resting Energy

This study compared whole-body leucine kinetics in endurance-trained (TRN) and sedentary (SED) control subjects. Eleven men and women (6 TRN, 5 SED) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine. Leucine turnover and oxidation were measured using tracer dilution and by measuring 13C enrichment of expired CO2 combined with respiratory calorimetry. Whole-body leucine turnover was greater in the TRN subjects (P less than 0.004; TRN 98.3 +/- 5.0, SED 75.3 +/- 4.2 mumol.kg-1.h-1; mean +/- SE), but there was no difference between groups in leucine oxidation (TRN 13.1 +/- 0.97, SED 11.5 +/- 0.48 mumol.kg-1.h-1). Thus more leucine turnover was available for nonoxidative utilization. In addition, the TRN subjects had higher resting energy expenditures compared with the SED group, and when all subjects were included in the analysis, there was a significant correlation between energy expenditure and protein turnover (n = 11, R = 0.61, P = 0.05). Therefore the heightened resting energy expenditure in the TRN subjects may be accounted for by an increased whole-body protein turnover. These results suggest that endurance training results in increased leucine and/or protein turnover, which may contribute to the increased resting energy expenditure observed in these subjects.

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Increased bone turnover is associated with protein and energy metabolism in adolescents with sickle cell anemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.280.3.e518 ◽

2001 ◽

Vol 280 (3) ◽

pp. E518-E527 ◽

Cited By ~ 11

Author(s):

Maciej S. Buchowski ◽

F. Alexander de la Fuente ◽

Paul J. Flakoll ◽

Kong Y. Chen ◽

Ernest A. Turner

Keyword(s):

Energy Expenditure ◽

Bone Turnover ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Protein Turnover ◽

Type I Collagen ◽

Whole Body ◽

Type I ◽

Protein Breakdown ◽

Body Protein

Contribution of bone turnover to the hypercatabolic state observed in sickle cell anemia is unknown. We examined the association between markers of bone turnover and basal rates of whole body protein turnover and energy expenditure in 28 adolescents with homozygous sickle cell anemia (HbSS) and in 26 matched controls with normal phenotype (HbAA). Whole body protein breakdown and synthesis were measured using a stable isotope of [15N]glycine, resting energy expenditure was measured by whole room indirect calorimetry, and the rate of pyridinoline cross-link (PYD) excretion in urine and fasting serum levels of the type I procollagen carboxy-terminal propeptide (PICP) were measured with commercial kits. Urinary PYD and serum PICP were significantly elevated in HbSS patients. The increase in procollagen synthesis, indicated by high levels of PICP, was significantly correlated with increased whole body protein synthesis. The increase in type I collagen degradation, indicated by high PYD excretion, was significantly correlated with increased protein breakdown. We conclude that increased rates of bone turnover contribute to the increased rates of protein turnover and energy expenditure observed in adolescents with homozygous sickle cell anemia.

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Muscle wasting in emphysema

Clinical Science ◽

10.1042/cs0750415 ◽

1988 ◽

Vol 75 (4) ◽

pp. 415-420 ◽

Cited By ~ 73

Author(s):

W. L. Morrison ◽

J. N. A. Gibson ◽

C. Scrimgeour ◽

M. J. Rennie

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Myofibrillar Protein ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

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