An acidic, heat-stable protein of molecular weight about 12,000 is one of the components of the enzyme system that catalyzes the reductive deamination of glycine (1, 2). The biological activity of this protein depends on the presence of 1 g-atom of covalently bound selenium per mol of protein (2, 3). Selenium also is known to be essential for the biological activity of mammalian (4) and avian (5) glutathione peroxidase and formate dehydrogenase of Escherichia coli (6-8) and various anaerobic bacteria (3, 9, 10). The selenium-containing moieties of these two enzymes have not been identified. In this communication evidence is presented that the organoselenium moiety of the clostridial glycine reductase selenoprotein is a selenocysteine residue. We have thus identified an essential selenium-containing residue in a protein. MATERIALS AND METHODSThe selenoprotein of the glycine reductase system was isolated from sonic extracts of Clostridium sticklandii (1, 2). Chromatography on Affi-Gel 501, a mercuribenzoate-agarose preparation supplied by Bio-Rad Laboratories, was used as a final isolation step for some preparations that were otherwise difficult to free of the last traces of impurities. * Cells grown in the presence of 1 ,uM Na275SeO3 and 2 mM Na2S were the source of the 75Se-labeled protein (2). The yeast extract and tryptone in the culture medium supplied additional sulfur, and the resultant high ratio of sulfur to selenium suppressed nonspecific substitution of the latter for sulfur in the proteins and other constituents of the cell.Other reagents were purchased as follows: carboxypeptidase Selenocystine was reduced to selenocysteine with KBH4, and the Se-carboxamidomethyl, Se-carboxymethyl, Se-carboxyethyl, and Se-aminoethyl derivatives of the selenol were prepared by procedures similar to those used for synthesis of the corresponding S-alkyl derivatives of cysteine (11). On cellulose thin-layer sheets these derivatives migrated with the following RF values: in 2-propanol/HCOOH/H20 (60:3:15) Se-carboxamidomethylselenocysteine, 0.18 and Se-carboxymethylselenocysteine, 0.35; in tertiary butyl alcohol/methylethylketone/88% HCOOH/H20 (40:30:15:15) Se-carboxymethylselenocysteine, 0.47, Se-carboxyethylselenocysteine, 0.50, and selenocystine, 0.1 in 1-propanol/5% NH40H (70:30) Se-carboxymethylselenocysteine, 0.44; in CHC13/CH30H/15% NH40H (40:40:10) Se-aminoethylselenocysteine, 0.46; and in 2-propanol/28% NH4OH/H20 (60:1.5:30) Se-aminoethylselenocysteine, 0.79, and selenocystine, 0.72. In each instance the RF of the corresponding sulfur compound was similar. RESULTSThe unusual absorption spectrum of the selenoprotein of glycine reductase (Fig. 1) is due to its high content of phenylalanine relative to tyrosine and to the absence of tryptophan. Almost identical spectra are exhibited by the parvalbumin of dogfish (12) and the calcium-binding protein component of troponin from rabbit muscle (13). The spectrum of the latter, like that of the selenoprotein, exhibits a shoulder in the 295-to 320-nm region. In neither insta...

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BACKGROUND & AIMS:Studies of the effects of direct oral anticoagulants (DOACs) in patients with cirrhosis have been limited by their small sample size, inclusion of patients with well-compensated cirrhosis, short follow-up times, inadequate validation of cirrhosis diagnoses, and non-standard definitions of bleeding. We aimed to systematically determine the characteristics, indications, and outcomes of patients with cirrhosis of all severity classes who received DOACs. METHODS:We performed a retrospective study of 138 patients with confirmed cirrhosis (93 with Child-Turcotte-Pugh scores of B or C) at a single center who started DOAC therapy (58,984 persondays; median, 181 days per patient) from September 2011 through April 2019. We collected data on clinical characteristics, indications for DOAC use, and outcomes. Standardized and validated definitions for bleeding complications were used. RESULTS:Twenty-nine patients (21%) stopped therapy due to a diagnosis of or perceived bleeding. The most common bleeding events were non-variceal upper and lower intestinal bleeding. No pretreatment laboratory parameters were associated with bleeding while patients received treatment, including platelet count (P [ .50), international normalized ratio (P [ .34), creatinine (P [ .27), and model for end-stage liver disease score (P [ .22). Frequency of bleeding events related to DOAC did not differ significantly among patients of different Child-Turcotte-Pugh classes (P [ .81), DOAC indications (P [ .60), or DOAC dosages (P [ .10).Higher proportions of patients with hepatocellular carcinoma (P [ .01) had major bleeding while receiving. CONCLUSIONS:Patients with decompensated cirrhosis have significant bleeding and rates of discontinuation of DOACs when they take them long term. Pretreatment laboratory parameters, DOAC dose, and Child-Turcotte-Pugh class were not associated with bleeding; hepatocellular carcinoma was associated with major bleeding.

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