Leucine metabolism in stable cirrhosis

K. D. Mullen, Scott Denne, A. J. McCullough, S. M. Savin, D. Bruno, A. S. Tavill, S. C. Kalhan

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 ± 17.1 vs. 138.3 ± 20.4 μmoles per liter, mean ± S.D., p <0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 ± 19.0 vs. 87.8 ± 19.0 μmoles per kg·hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 ± 2.5 vs. 12.7 ± 3.1 μmol per kg·hr, p <0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p <0.03). The plasma clearance rate of leucine was significantly increased in cirrhosis (903.5 ± 232.0 vs. 650.8 ± 164.4 ml per kg·hr, p <0.001), as was the fractional turnover rate of the free leucine pool (2.3 ± 0.5 vs. 1.6 ± 0.2% per min, p <0.02). Calculated rates of protein degradation and protein synthesis were similar in the two groups. These alterations in protein metabolism were associated with elevated serum levels of insulin (12.5 ± 7.6 vs. 5.9 ± 1.1 μunits per ml, p <0.03) and β-hydroxybutyrate (0.2 ± 0.6 vs. 0.13 ± 0.05 mM, p <0.05). Although the basal metabolic rates were similar in the two groups, the respiratory quotients were reduced in cirrhosis (0.75 ± 0.01 vs. 0.84 ± 0.03, p <0.001), suggesting an increased contribution of fat toward oxidative metabolism. Consistent with reduced leucine oxidation, urinary total urea nitrogen were also decreased in cirrhosis (p <0.01). Because total body water was similar in cirrhotics and controls (61.7 ± 6.1 vs. 58.4 ± 5.0% body weight), comparison of the data did not differ whether expressed per unit total body weight or per unit fat-free body mass. These data indicate plasma leucine concentrations may determine the rate of leucine oxidation. Consequently, the decreased rate of leucine oxidation in stable cirrhosis may be a consequence of decreased substrate availability. Although hyperinsulinemia was associated with decreased plasma leucine levels in cirrhosis, there was no significant difference in leucine or protein turnover between the cirrhosis and control groups.

Original languageEnglish (US)
Pages (from-to)622-630
Number of pages9
JournalHepatology
Volume6
Issue number4
StatePublished - 1986
Externally publishedYes

Fingerprint

Leucine
Fibrosis
Body Water
Fats
Proteins
Urea
Nitrogen
Body Weight
Hydroxybutyrates
Basal Metabolism
Branched Chain Amino Acids
Calorimetry
Hyperinsulinism
Ammonia
Oxygen Consumption
Proteolysis

ASJC Scopus subject areas

  • Hepatology

Cite this

Mullen, K. D., Denne, S., McCullough, A. J., Savin, S. M., Bruno, D., Tavill, A. S., & Kalhan, S. C. (1986). Leucine metabolism in stable cirrhosis. Hepatology, 6(4), 622-630.

Leucine metabolism in stable cirrhosis. / Mullen, K. D.; Denne, Scott; McCullough, A. J.; Savin, S. M.; Bruno, D.; Tavill, A. S.; Kalhan, S. C.

In: Hepatology, Vol. 6, No. 4, 1986, p. 622-630.

Research output: Contribution to journalArticle

Mullen, KD, Denne, S, McCullough, AJ, Savin, SM, Bruno, D, Tavill, AS & Kalhan, SC 1986, 'Leucine metabolism in stable cirrhosis', Hepatology, vol. 6, no. 4, pp. 622-630.
Mullen KD, Denne S, McCullough AJ, Savin SM, Bruno D, Tavill AS et al. Leucine metabolism in stable cirrhosis. Hepatology. 1986;6(4):622-630.
Mullen, K. D. ; Denne, Scott ; McCullough, A. J. ; Savin, S. M. ; Bruno, D. ; Tavill, A. S. ; Kalhan, S. C. / Leucine metabolism in stable cirrhosis. In: Hepatology. 1986 ; Vol. 6, No. 4. pp. 622-630.
@article{5e79cc4868f74512972c72d569538aff,
title = "Leucine metabolism in stable cirrhosis",
abstract = "Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 ± 17.1 vs. 138.3 ± 20.4 μmoles per liter, mean ± S.D., p <0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 ± 19.0 vs. 87.8 ± 19.0 μmoles per kg·hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 ± 2.5 vs. 12.7 ± 3.1 μmol per kg·hr, p <0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p <0.03). The plasma clearance rate of leucine was significantly increased in cirrhosis (903.5 ± 232.0 vs. 650.8 ± 164.4 ml per kg·hr, p <0.001), as was the fractional turnover rate of the free leucine pool (2.3 ± 0.5 vs. 1.6 ± 0.2{\%} per min, p <0.02). Calculated rates of protein degradation and protein synthesis were similar in the two groups. These alterations in protein metabolism were associated with elevated serum levels of insulin (12.5 ± 7.6 vs. 5.9 ± 1.1 μunits per ml, p <0.03) and β-hydroxybutyrate (0.2 ± 0.6 vs. 0.13 ± 0.05 mM, p <0.05). Although the basal metabolic rates were similar in the two groups, the respiratory quotients were reduced in cirrhosis (0.75 ± 0.01 vs. 0.84 ± 0.03, p <0.001), suggesting an increased contribution of fat toward oxidative metabolism. Consistent with reduced leucine oxidation, urinary total urea nitrogen were also decreased in cirrhosis (p <0.01). Because total body water was similar in cirrhotics and controls (61.7 ± 6.1 vs. 58.4 ± 5.0{\%} body weight), comparison of the data did not differ whether expressed per unit total body weight or per unit fat-free body mass. These data indicate plasma leucine concentrations may determine the rate of leucine oxidation. Consequently, the decreased rate of leucine oxidation in stable cirrhosis may be a consequence of decreased substrate availability. Although hyperinsulinemia was associated with decreased plasma leucine levels in cirrhosis, there was no significant difference in leucine or protein turnover between the cirrhosis and control groups.",
author = "Mullen, {K. D.} and Scott Denne and McCullough, {A. J.} and Savin, {S. M.} and D. Bruno and Tavill, {A. S.} and Kalhan, {S. C.}",
year = "1986",
language = "English (US)",
volume = "6",
pages = "622--630",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Leucine metabolism in stable cirrhosis

AU - Mullen, K. D.

AU - Denne, Scott

AU - McCullough, A. J.

AU - Savin, S. M.

AU - Bruno, D.

AU - Tavill, A. S.

AU - Kalhan, S. C.

PY - 1986

Y1 - 1986

N2 - Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 ± 17.1 vs. 138.3 ± 20.4 μmoles per liter, mean ± S.D., p <0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 ± 19.0 vs. 87.8 ± 19.0 μmoles per kg·hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 ± 2.5 vs. 12.7 ± 3.1 μmol per kg·hr, p <0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p <0.03). The plasma clearance rate of leucine was significantly increased in cirrhosis (903.5 ± 232.0 vs. 650.8 ± 164.4 ml per kg·hr, p <0.001), as was the fractional turnover rate of the free leucine pool (2.3 ± 0.5 vs. 1.6 ± 0.2% per min, p <0.02). Calculated rates of protein degradation and protein synthesis were similar in the two groups. These alterations in protein metabolism were associated with elevated serum levels of insulin (12.5 ± 7.6 vs. 5.9 ± 1.1 μunits per ml, p <0.03) and β-hydroxybutyrate (0.2 ± 0.6 vs. 0.13 ± 0.05 mM, p <0.05). Although the basal metabolic rates were similar in the two groups, the respiratory quotients were reduced in cirrhosis (0.75 ± 0.01 vs. 0.84 ± 0.03, p <0.001), suggesting an increased contribution of fat toward oxidative metabolism. Consistent with reduced leucine oxidation, urinary total urea nitrogen were also decreased in cirrhosis (p <0.01). Because total body water was similar in cirrhotics and controls (61.7 ± 6.1 vs. 58.4 ± 5.0% body weight), comparison of the data did not differ whether expressed per unit total body weight or per unit fat-free body mass. These data indicate plasma leucine concentrations may determine the rate of leucine oxidation. Consequently, the decreased rate of leucine oxidation in stable cirrhosis may be a consequence of decreased substrate availability. Although hyperinsulinemia was associated with decreased plasma leucine levels in cirrhosis, there was no significant difference in leucine or protein turnover between the cirrhosis and control groups.

AB - Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 ± 17.1 vs. 138.3 ± 20.4 μmoles per liter, mean ± S.D., p <0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 ± 19.0 vs. 87.8 ± 19.0 μmoles per kg·hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 ± 2.5 vs. 12.7 ± 3.1 μmol per kg·hr, p <0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p <0.03). The plasma clearance rate of leucine was significantly increased in cirrhosis (903.5 ± 232.0 vs. 650.8 ± 164.4 ml per kg·hr, p <0.001), as was the fractional turnover rate of the free leucine pool (2.3 ± 0.5 vs. 1.6 ± 0.2% per min, p <0.02). Calculated rates of protein degradation and protein synthesis were similar in the two groups. These alterations in protein metabolism were associated with elevated serum levels of insulin (12.5 ± 7.6 vs. 5.9 ± 1.1 μunits per ml, p <0.03) and β-hydroxybutyrate (0.2 ± 0.6 vs. 0.13 ± 0.05 mM, p <0.05). Although the basal metabolic rates were similar in the two groups, the respiratory quotients were reduced in cirrhosis (0.75 ± 0.01 vs. 0.84 ± 0.03, p <0.001), suggesting an increased contribution of fat toward oxidative metabolism. Consistent with reduced leucine oxidation, urinary total urea nitrogen were also decreased in cirrhosis (p <0.01). Because total body water was similar in cirrhotics and controls (61.7 ± 6.1 vs. 58.4 ± 5.0% body weight), comparison of the data did not differ whether expressed per unit total body weight or per unit fat-free body mass. These data indicate plasma leucine concentrations may determine the rate of leucine oxidation. Consequently, the decreased rate of leucine oxidation in stable cirrhosis may be a consequence of decreased substrate availability. Although hyperinsulinemia was associated with decreased plasma leucine levels in cirrhosis, there was no significant difference in leucine or protein turnover between the cirrhosis and control groups.

UR - http://www.scopus.com/inward/record.url?scp=0022551815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022551815&partnerID=8YFLogxK

M3 - Article

C2 - 3089896

AN - SCOPUS:0022551815

VL - 6

SP - 622

EP - 630

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -