Small-intestinal mucosal protein synthesis and whole-body protein turnover in alcoholic liver disease.
We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2. 58+/-0.32%.h(-1) (mean+/-S.D.) in the normal subjects and 2.04+/-0. 18%.h(-1) in the ALD patients (P<0.003), despite the fact that the protein synthetic capacity (microgram of RNA/mg of protein) was higher in ALD patients (160+/-14 compared with 137+/-6 microgram/mg; P<0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23+/-0.91 compared with 13+/-2.2 microgram/mg; P<0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204+/-18 and 196+/-44 micromol leucine.h(-1).kg(-1) for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.
Nakshabendi
I M
IM
Department of Gastroenterology, Royal Infirmary, Glasgow, Scotland, U.K.
Downie
S
S
Russell
R I
RI
Rennie
M J
MJ
D000328:Adult; D000428:Alcohol Drinking; D002247:Carbon Isotopes; D016022:Case-Control Studies; D048429:Cell Size; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small; D007930:Leucine; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis
D002247:Carbon Isotopes; D007930:Leucine