Abstract
S-Adenosylmethionine (AdoMet) is metabolized through three main pathways, i.e. (a) transfer of its methyl group to a variety of methyl acceptors, (b) decarboxylation followed by aminopropylation leading to polyamine synthesis, and (c) cleavage of the bond between the sulfur atom and carbon 4 of the amino acid chain, resulting in formation of methylthioadenosine and homoserine thiolactone. In this study the metabolism of AdoMet through these pathways was studied after intravenous administration to rats of [1-14C]-, [3,4-14C]-, [methyl-14C]-, and [35S]AdoMet at various doses. The relative utilization of AdoMet and methionine was also investigated. The results show that intravenously administered AdoMet is efficiently metabolized in vivo up to the highest tested dose (250 mumol X kg-1 body weight), about two-thirds of the metabolized compound being utilized via transmethylation and cleavage to methylthioadenosine and one-third via decarboxylation. The efficient incorporation of the methyl group of AdoMet into muscle creatine indicates unambiguously that the compound is taken up and metabolized by the liver. Moreover, intravenously administered AdoMet is shown to be a better precursor than methionine both in creatine formation and in the utilization of the sulfur atom in transsulfuration reactions.
Highlights
From the BwResearch Co., Research Laboratories, Liscate (Milurn), Italy and the $Department ofMedical Chemistryand Biochemistry, University ofMilun, Italy
Utilization of AdoMet for Creatine Synthesis-From the results reported by Mudd and Poole [29] it can be calculated that more than 80%of the methionine methyl group utilized for methylations is involvedin the synthesis of creatine
Radioactive creatinine accounted for a small percentage of total urinary radioactivity (Table 111) both with methionine and AdoMet, since a large fraction of radioactivity is associated with other methylated metabolites and with unchanged compounds and because urinary creatinine is derived from the nonenzymatic conversion of creatine phosphate, a conversion that proceeds at the rate of about 2% of total creatine phosphate/day
Summary
When radioactive AdoMet was purified, aliquots of the eluted measured in a 1-ml sample added to 10 ml of Lumagel. Trichloroacetic acid was removed from the supernatant by washing AdoMet and [methyl-"C]Met and with [%]AdoMet were frozen in three times with diethyl ether previously shaken with a 20% FeSO, liquid nitrogen and powdered in a mortar. Supernawas determined using either ["Cltoluene or Na2?30, Lipophilic compounds were extracted from the pellet with 95% collected in 1ml of 1N HC1 to avoid AdoMet decomposition.Tissues ethanol containing 1.5% sodium acetate (8 ml, twice), with absolute to be analyzed were dissected immediately after sacrifice and frozen ethanol (8 ml, three times), and ch1oroform:methanol
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