EFFECT OF S-ADENOSYLMETHIONINE (SAMe) ON PLASMA LEVELS OF SULFUR-CONTAINING AMINO ACIDS (SCAA) IN PATIENTS WITH LIVER CIRRHOSIS

G. Marchesini, G.P. Bianchi, R. Lolli, M. Zoli, E. Pisi: Istituto di Clinica Medica Generale e Terapia, Policlinico S. Orsola, Bologna, Italy

The impairment of the transsulfuration pathway may contribute to the low glutathione content found in the hepatocytes of patients with liver cirrhosis. The defective metabolic step is located at the level of SAMe formation from methionine (Hepatology 1988;8:65-8). SAMe administration was reported to increase l iver glutathione. In this study we measured the plasma SCAA in 8 c i rrhot ic patients given SAMe (1.2 g/day i .v . for 3 days, followed by oral administration of 1.2 g/day for additional 30 days). All patients had severe hepatocellular fa i lure (Mean [ range ] : Albumin, 3.2 g/dL [ 2.4-4.3 ] ; B i l i rubin, 4.1 mg/dL [ 0.5-22.7 ] ; Prothrombin act iv i ty , 53% [ 26-86 I ; Galactose elimination, 3.69 mg/kg/min [ 3.06-4.33 I ) and received a daily diet containing at least 1800 kcal and l g/kg body w~ protein. Eight pair-matched cirrhotics served as controls. Following 3 days of i . v . SAMe no changes in plasma amino acids were observed. On the other hand, after 30 days of oral SAMe administration plasma cystine increased from 36.3 [ SD 35.01 ] pmol/L to 63.9 [ 74.9 ] (p < 0.05; Dunnett test) and taurine from 43.3 [ 25.0 ] pmol to 72.5 [ 47.4 ] (p < O.Ol). Methionine decreased from 129.6 [ 107.1 ] pmol/L to 82.1 [ 33.6 ] (ns). No signif icant changes in branched-chain or aromatic amino acids were found. Similarly, no changes in SCAA were observed in che control group. These data are consistent with an effect of long-term oral SAMe on SCAA, which may be related to i ts capabil ity to bypass the rate- l imit ing step of SAMe synthetase and to provide substrates for glutathione formation. Moreover, no detrimental effects on plasma methionine levels were documented after SAMe.

BILE ACID N-ACETYLGLUCOSAMINIDES: A NOVEL FORM OF CONJUGATION IN MAN

H.-U. Marschall, G. Green~ B. Egestad, H. Matern, S. Matern~ and J. Sj~vall. Department of Internal Medicine II!, Hedical Faculty, Aachen University of Technology, D-5100 Aachen, and Department of Physiological Chemistry, Karolinska Institutet, S-I0401 Stockholm.

Glucosides of bile acids were recently identified in human urine. In order to analyse the patterns of these compounds in detail, non-amidated and glycine- and taurine-conjugated bile acids, isolated by ion exchange chromatography on Lipidex-DEAP, were separated into individual compounds using a re~rersed-phase HPLC-system. Each HPLC-Fraction was analysed by fast atom bombardment (FAB) mass spectrometry of the underivatized substances and by GC/MS of the methyl ester trimethylsilyl ether derivatives, prepared after hydrolysis with cholyl- glycine hydrolase. The GC/MS analyses showed fragments typical for N-acetyl- hexosaminides (m/z 173 and 186) in addition to those also given by glucoside derivatives (m/z 204 and 217). The negative ion FAB spectra showed quasimo!e- cular ions at m/z 592, 594 and 610 consistent with N-acetylhexosaminides of unsaturated dihydroxy and saturated di- and trihydroxy bile acids. These com- pounds were inert towards ~- and/~-glucosidase but were cleaved completely with N-acetylglucosaminidase. The liberated bile acids did not belong to the common primary or secundary bile acids. FAB-MS analyses of the glycine- and taurine- conjugated bile acid glycosides showed only ions consistent with amidated tri- hydroxy bile acid glycosides (m/z 626 and 676). These compounds were cleaved only by/~glucosidase, the liberated bile acids yielded unknown fragmentation patterns in GC/MS. The daily excretion of non-amidated bile acid glucosides was about i0 pg, of glycine- and taurine-conjugated bile acid glucosides 122 pg and of non-amidat~ N-acetylglucosaminides about i00 pg, as determined by com- parison to added ±oC-labelled chenodeoxycholic acid glucoside as int. standard.

$148