Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

TY - JOUR

T1 - Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

AU - Dam, Gitte

AU - Keiding, Susanne

AU - Munk, Ole Lajord

AU - Ott, Peter

AU - Buhl, Mads

AU - Vilstrup, Hendrik

AU - Bak, Lasse Kristoffer

AU - Waagepetersen, Helle Sønderby

AU - Schousboe, Arne

AU - Møller, Niels

AU - Sørensen, Michael

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Branched-chain amino acids(BCAA) are used in attempts to reduce blood ammonia inpatients with cirrhosis and intermittent hepatic encephalopathybased on the hypothesis that BCAA stimulate muscle ammoniadetoxification. We studied the effects of an oral dose of BCAA onthe skeletal muscle metabolism of ammonia and amino acids in 14patients with cirrhosis and in 7 healthy subjects by combining[13N]ammonia positron emission tomography (PET) of the thighmuscle with measurements of blood flow and arteriovenous (A-V)concentrations of ammonia and amino acids. PET was used tomeasure the metabolism of blood-supplied ammonia and the A-Vmeasurements were used to measure the total ammonia metabolismacross the thigh muscle. After intake of BCAA, blood ammoniaincreased more than 30% in both groups of subjects (both P <0.05). Muscle clearance of blood-supplied ammonia (PET) wasunaffected (P < 0.75), but the metabolic removal rate (PET)increased significantly because of increased blood ammonia inboth groups (all P < 0.05). The total ammonia clearance across theleg muscle (A-V) increased by more than 50% in both groups, andthe flux (A-V) of ammonia increased by more than 45% (all P <0.05). BCAA intake led to a massive glutamine release from themuscle (cirrhotic patients, P < 0.05; healthy subjects, P < 0.12).In conclusion, BCAA enhanced the intrinsic muscle metabolism ofammonia but not the metabolism of blood-supplied ammonia inboth the patients with cirrhosis and in the healthy subjects.

AB - Branched-chain amino acids(BCAA) are used in attempts to reduce blood ammonia inpatients with cirrhosis and intermittent hepatic encephalopathybased on the hypothesis that BCAA stimulate muscle ammoniadetoxification. We studied the effects of an oral dose of BCAA onthe skeletal muscle metabolism of ammonia and amino acids in 14patients with cirrhosis and in 7 healthy subjects by combining[13N]ammonia positron emission tomography (PET) of the thighmuscle with measurements of blood flow and arteriovenous (A-V)concentrations of ammonia and amino acids. PET was used tomeasure the metabolism of blood-supplied ammonia and the A-Vmeasurements were used to measure the total ammonia metabolismacross the thigh muscle. After intake of BCAA, blood ammoniaincreased more than 30% in both groups of subjects (both P <0.05). Muscle clearance of blood-supplied ammonia (PET) wasunaffected (P < 0.75), but the metabolic removal rate (PET)increased significantly because of increased blood ammonia inboth groups (all P < 0.05). The total ammonia clearance across theleg muscle (A-V) increased by more than 50% in both groups, andthe flux (A-V) of ammonia increased by more than 45% (all P <0.05). BCAA intake led to a massive glutamine release from themuscle (cirrhotic patients, P < 0.05; healthy subjects, P < 0.12).In conclusion, BCAA enhanced the intrinsic muscle metabolism ofammonia but not the metabolism of blood-supplied ammonia inboth the patients with cirrhosis and in the healthy subjects.

KW - Amino Acids, Branched-Chain

KW - Ammonia

KW - Female

KW - Femoral Artery

KW - Femoral Vein

KW - Glutamine

KW - Humans

KW - Isoleucine

KW - Leucine

KW - Liver Cirrhosis, Alcoholic

KW - Male

KW - Metabolic Clearance Rate

KW - Middle Aged

KW - Muscle, Skeletal

KW - Positron-Emission Tomography

KW - Radial Artery

KW - Regional Blood Flow

KW - Thigh

KW - Tomography, X-Ray Computed

KW - Valine

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1152/ajpgi.00062.2011

DO - 10.1152/ajpgi.00062.2011

M3 - Journal article

C2 - 21636533

SN - 0193-1857

VL - 301

SP - G269-77

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

IS - 2

ER -