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Title: Leucine metabolism in patients with Hepatic Encephalopathy

Abstract

A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.

Authors:
; ; ;
Publication Date:
Research Org.:
Florida State Univ., Tallahassee
OSTI Identifier:
5318671
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 86-028530
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; LEUCINE; METABOLISM; LIVER CIRRHOSIS; PATHOGENESIS; PROTEINS; BIOSYNTHESIS; CARBON 13; CARBON DIOXIDE; MASS SPECTROSCOPY; NITROGEN 15; PATIENTS; TRACER TECHNIQUES; AMINO ACIDS; CARBON COMPOUNDS; CARBON ISOTOPES; CARBON OXIDES; CARBOXYLIC ACIDS; CHALCOGENIDES; DIGESTIVE SYSTEM DISEASES; DISEASES; EVEN-ODD NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; NITROGEN ISOTOPES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; OXIDES; OXYGEN COMPOUNDS; SPECTROSCOPY; STABLE ISOTOPES; SYNTHESIS; 550901* - Pathology- Tracer Techniques

Citation Formats

McGhee, A.S., Kassouny, M.E., Matthews, D.E., and Millikan, W. Leucine metabolism in patients with Hepatic Encephalopathy. United States: N. p., 1986. Web.
McGhee, A.S., Kassouny, M.E., Matthews, D.E., & Millikan, W. Leucine metabolism in patients with Hepatic Encephalopathy. United States.
McGhee, A.S., Kassouny, M.E., Matthews, D.E., and Millikan, W. Sat . "Leucine metabolism in patients with Hepatic Encephalopathy". United States. doi:.
@article{osti_5318671,
title = {Leucine metabolism in patients with Hepatic Encephalopathy},
author = {McGhee, A.S. and Kassouny, M.E. and Matthews, D.E. and Millikan, W.},
abstractNote = {A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:3,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 1986},
month = {Sat Mar 01 00:00:00 EST 1986}
}

Conference:
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  • The purpose of this study was to determine whether increased oxidation of or protein synthesis requiring leucine occurs in cirrhotic patients. Five control subjects and four subjects with cirrhosis were equilibrated on a baseline diet (0.6 g protein per kg ideal body weight (IBW)) with sufficient nonprotein calories to preclude negative nitrogen balance. An additional four patients were equilibrated on the same type of diet with a higher protein level (0.75 g per kg IBW). Control subjects and the patients were then studied during continuous infusion of L-(/sup 15/N, 1-/sup 13/C) leucine in the fasted state and, in the fedmore » state, with a Propac diet which had the same distribution of energy nutrients as the baseline diets. Plasma levels of L-(/sup 15/N, 1-/sup 13/C), L-(1-/sup 13/C) and L-(/sup 15/N) leucine were measured during isotopic steady state by gas chromatography-mass spectrometry and fractional excretion of /sup 13/CO/sup 2/ in breath samples were analyzed by isotopic ratio mass spectrometry. During the fasted and fed states leucine metabolism was measured to quantitate rates of nitrogen flux (Q/sub N/), carbon flux (Q/sub c/) and oxidation to carbon dioxide and water (C). From these measured values, proteins breakdown (B), protein synthesis (S), deamination (X/sup 0/) and reamination (X/sub N/) were calculated. The results showed that protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW and maintenance level of nonprotein calories. The data also showed that leucine metabolism can be quantitatively and reproducibly measured in subjects with cirrhosis.« less
  • The integrity of GABA-A receptors and of central benzodiazepine receptors was evaluated in membrane preparations from prefrontal cortex and caudate nuclei obtained at autopsy from nine cirrhotic patients who died in hepatic coma and an equal number of age-matched control subjects. Histopathological studies revealed Alzheimer Type II astrocytosis in all cases in the cirrhotic group; controls were free from neurological, psychiatric or hepatic diseases. Binding to GABA-A receptors was studied using (/sup 3/H)muscimol as radioligand. The integrity of central benzodiazepine receptors was evaluated using (/sup 3/H)flunitrazepam and (/sup 3/H)Ro15-1788. Data from saturation binding assays was analyzed by Scatchard plot. Nomore » modifications of either affinities (Kd) or densities (Bmax) of (/sup 3/H)muscimol of central benzodiazepine binding sites were observed. These findings do not support recent suggestions that alterations of either high-affinity GABA or benzodiazepine receptors play a significant role in the pathogenesis of hepatic encephalopathy.« less
  • Purpose. To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). Methods. Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. Results. After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoringmore » or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. Conclusion. Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.« less
  • We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significantmore » differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.« less
  • The role of the splanchnic bed in the economy of whole body leucine (leu) metabolism was assessed in 5 chronically catheterized conscious fasting mongrel dogs. Using primed continuous intravenous infusions of L-(/sup 15/N, 1-/sup 13/C)-leu and L-1-/sup 14/C-leu the metabolic fate of leu carbon (C) and nitrogen (N) in the splanchnic region was compared with that in the body as a whole, by measurement of isotope and substrate balance across gut and liver. Sampling was from the portal and hepatic veins and arch of aorta. Blood flow estimation was made by dye dilution. Whole body leu N and C fluxesmore » and oxidation were (Mean +/- SEM); 453 +/ 47, 197 +/- 37 and 41 +/- 5 ..mu..mol kg-1.h-1, respectively. The splanchnic bed accounted for (% of whole body) 36 +/- 13 of leu disappearance into proteins (liver 14%; gut 22%); 24 +/- 7 of leu appearance via protein breakdown (liver 8%; gut 16%) 12 +/- 2% of leu transamination to ..cap alpha..-ketoisocaproate (KIC) (liver 7%; gut 5%); 12 +/- 3 of KIC reamination to leu (liver 7%; gut 5%) and 11 +/- 3 of leu oxidation (liver 2%; gut 9%). Hence, in the fasting state the splanchnic region accounts for a small proportion of whole body leu-KIC interconversion and oxidation, but a more significant proportion of whole body of leu for protein synthesis.« less