Regular Paper| Volume 20, ISSUE 1, P138-142, 1994

Nicotinamide methylation in patients with cirrhosis

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      Methylation reactions play an important role in the transformation of endogenous and exogenous substances. Up to 85% of all transmethylation reactions occur in the liver. Several studies have shown that these metabolic processes are greatly influenced by the presence of hepatic diseases. We investigated the methylation of nicotinamide in 16 control subjects and in 29 patients with cirrhosis (19 Child A, 10 Child B). The basal serum value of N-methyl-nicotinamide was measured in all subjects. In seven controls and in nine patients with cirrhosis (5 Child A and 4 Child B), the serum levels and urinary excretion (5 and 24 h) of N-methyl-nicotinamide were also evaluated after oral administration of nicotinamide (1.5 mg/kg body weight). The basal serum levels of N-methyl-nicotinamide were significantly (p<0.05) higher in patients with cirrhosis (Child A: median 34 ng/ml, 16th percentile 24, 84th percentile 61; Child B median 45, 16th percentile 34, 84th percentile 81) than in controls (median 22, 16th percentile 13, 85th percentile 28). After the nicotinamide load the urinary excretion and the time course of serum N-methyl-nicotinamide in cirrhosis were also higher (p<0.05) than in controls (24 h urinary excretion=66.2 mg±5 S.D. in cirrhosis; 47.2±10.3 in controls) (area under the serum concentration versus time curve=68 μg·ml−1·min−1±22 S.D. in cirrhosis; 32±15 in controls). In conclusion, our results show that cirrhosis does not impair the efficiency of nicotinamide methylation.

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        • Horowitz JH
        • Rypins EB
        • Henderson JM
        • et al.
        Evidence for impairment of transulfuration pathway in cirrhosis.
        Gastroenterology. 1981; 81: 668-675
        • Duce AM
        • Ortiz P
        • Cabrero C
        • Mato JM
        S-Adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis.
        Hepatology. 1988; 8: 65-68
        • Geubel AP
        • Mairlot MC
        • Buchet JP
        • Dive C
        • Lauwerys R
        Abnormal methylation capacity in human liver cirrhosis.
        Int J Clin Pharm Res. 1988; VIII: 117-122
        • Hankes LV
        Nicotinic acid and nicotinamide.
        in: Tannenbaum SR Walstra P Handbook of Vitamins. Machlin, New Jersey1984: 329-377
        • Jenkes BH
        • McKee WR
        • Swendseid ME
        • Faraji B
        • Figueroa WG
        • Clemens RA
        Methylation main derivatives in plasma and urine after an oral dose of nicotinamide given to subject fed a low methionine diet.
        Am J Clin Nutr. 1987; 46: 496-502
        • Hoshino J
        • Kune I
        • Kroger H
        Methylation of nicotinamide in rat liver cytosol and its correlation with hepatocellular proliferation.
        Biochem Biophys Acta. 1982; 719: 518-522
        • Frezza M
        • Pozzato G
        • Tritapepe R
        • Di Padova C
        Prevention by S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women.
        Am J Gastroenterol. 1988; 83: 1098-1102
        • Vendemiale G
        • Altomare E
        • Trizio T
        • et al.
        Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease.
        Scand J Gastroenterol. 1989; 24: 407-415
        • Tygstrup N
        Determination of hepatic elimination capacity (Lm) of galactose by single injection.
        Scand J Clin Lab Invest. 1966; 18: 118-125
        • Somogy A
        • Siebert D
        • Bochner F
        Determination of endogenous concentrations of N1-methylnicotinamide in human plasma and urine by high performance liquid chromatography.
        Anal Biochem. 1990; 187: 160-165
        • Pelletier O
        • Brassard R
        Automated and manual determination of N-methylnicotinamide in urine.
        J Clin Nutr. 1977; 30: 2108-2116
        • Clark BR
        Fluorimetric quantitation of picomole amounts of N1-methylnicotinamide and nicotinamide in serum.
        Methods in Enzymology. 1980; 66: 5-8
        • Clark BR
        • Halfem RM
        • Smith RA
        A fluorimetric method for quantitation in the picomole range of methylnicotinamide and nicotinamide in serum.
        Anal Bioch. 1975; 68: 54-61
        • Cantoni GL
        Biological methylation: selected aspects.
        Ann Rev Biochem. 1975; 44: 435-451
        • Weisger RA
        • Jakoby WD
        S-methylation: thiol S-methyl-transferase.
        in: Enzymatic Basis of Detoxication. Vol II. Academic Press Inc, San Diego, California1980: 131-140
        • McFadden PN
        • Clarke S
        Conversion of isoaspartyl peptides to normal peptides: implications for the cellular repair of damaged proteins.
        in: Proc Natl Acad Sci USA. 48. 1987: 2595-2599
        • Hirata F
        • Axelrod J
        Phospholipid methylation and biological signal transmission.
        Science. 1980; 209: 1082-1090
        • Razin A
        • Riggs AD
        DNA methylation and gene function.
        Science. 1980; 218: 604-610
        • Felsenfeld G
        • McGee JD
        Methylation and gene control.
        Nature. 1982; 296: 602-603
        • Doerfler W
        DNA methylation and gene activity.
        Ann Rev Biochem. 1983; 52: 93-124
        • Boehm TL
        • Drahovsky D
        Alterations of enzymatic methylation of DNA cytosines by chemical carcinogens: a mechanism involved in the initiation of carcinogenesis.
        JNCI. 1983; 71: 429-433
        • Aiba N
        • Nambu S
        • Inoue K
        • Sasaki H
        Hypomethylation of the c-myc oncogene in liver cirrhosis and chronic hepatitis.
        Gastroenterol Jpn. 1989; 24: 270-276
      1. Dietary methyl groups and cancer (Review Article).
        Nutr Rev. 1986; 44: 278-280
        • Mudd SH
        • Poole JR
        Labile methyl balances for normal humans on various dietary regimens.
        Metabolism. 1975; 24: 721-735
        • Mainardi L
        • Nicolis FB
        • Tenconi LT
        Eliminazione urinaria di N1-metilnicotinamide e di N1-metil-piridone-5-carbossamide nell'uomo: variazioni in funzione del sesso e dell'eta.
        Acta Vitaminologica. 1962; 16: 255-262
        • Lentner C.
        Units of measurement, body fluids, composition of the body, nutrition.
        in: Lentner C Lentner C Wink A Geigy Scientific Tables. Geigy, Basle, Switzerland1981: 94
        • Stanulovic M
        • Chaykin S
        Metabolic origins of the pyridones of N-methylnicotinamide in man and rat.
        Arch Biochem Biophys. 1971; 145: 35-42
        • Fox IH
        Adenosine triphosphate degradation in specific disease.
        J Lab Clin Med. 1985; 106: 101-110
        • Budillon G
        • Citarella C
        • Loguercio C
        • Nardone G
        • Sicolo P
        • Del Vecchio Blanco C
        Hyperuricemia induced by fructose load in liver cirrhosis.
        Ital J Gastroenterol. 1992; 24: 373-377
        • Matthewson K
        • Record CO
        Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease.
        Clin Sci. 1986; 70: 295-299