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Partitioning of [methyl‐3H]methionine to methylated products under normal and high demand conditions in young Yucatan miniature pigs
Author(s) -
McBreairty Laura E,
Lamarre Simon G,
McGowan Ross A,
Bertolo Robert F
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.740.33
Subject(s) - creatine , methionine , sarcosine , chemistry , choline , methylation , biochemistry , methyl group , metabolism , dna synthesis , medicine , endocrinology , dna , biology , amino acid , organic chemistry , glycine , alkyl
Methionine is the main source of 1‐carbon molecules which are partitioned to synthesize various methylated products including creatine, phosphatidylcholine, sarcosine and methylated DNA. Guanidinoacetate (GAA) is methylated to form creatine and because hepatic creatine synthesis in rats appears to be proportional to GAA availability, we hypothesized that when GAA is in excess, increased creatine synthesis will create a higher demand for available methyl groups. The objective of this study was to characterize the partitioning of the methyl groups of methionine with or without excess GAA. Anaesthetized piglets (15–18 d old) were intraportally infused with either GAA (n=5) or saline (n=5) for 2 h. A bolus of [methyl‐ 3 H]methionine was intraportally infused at 1 h and liver samples were excised by cautery 30, 45 and 60 min later. Various methylated metabolites in the liver were analyzed for specific activity. As hypothesized, excess GAA led to increased creatine synthesis, resulting in a ~200% increase in methyl‐ 3 H incorporation (P<0.05). We further hypothesized that this increased creatine synthesis would attenuate methyl‐ 3 H incorporation into other products. However, incorporation into DNA was ~240% greater with GAA (P<0.05). In neonatal piglets, creatine synthesis is increased by excess GAA availability but instead of sequestering available methyl groups, this led to increased methylation of DNA. (CIHR)