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Hepatic Creatine Synthesis in the Rat
Author(s) -
Silva Robin Paul da,
Brosnan John T,
Brosnan Margaret E
Publication year - 2007
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.21.6.a1324-c
Subject(s) - creatine , methionine , in vivo , glycine , medicine , arginine , de novo synthesis , chemistry , choline , endocrinology , betaine , homocysteine , creatinine , biochemistry , metabolism , enzyme , biology , amino acid , microbiology and biotechnology
Cr (Cr) and Cr‐phosphate play a key role in energy metabolism. Approximately 1.7% of the body’s total Cr is lost by cyclization to creatinine per day. Replacement of this Cr occurs via a combination of diet and synthesis. Cr synthesis requires just two enzymes, arginine:glycine amidinotransferase (AGAT) which catalyzes the formation of guanidinoacetate (GAA) from glycine and arginine, and guanidinoacetate N‐methyltransferase (GAMT) which employs S‐adenosylmethionine to methylate GAA to Cr. In the rat, high activities of AGAT are found in the kidney and of GAMT in the liver which suggests the occurrence of an inter‐organ pathway for Cr synthesis. We have, therefore, investigated Cr synthesis by rat liver, both in vivo and in vitro. Rat hepatocytes produce Cr from GAA and this is increased by incubation with methyl group donors, methionine or betaine with homocysteine. Hepatic GAA uptake in vivo was determined in rats fed a Cr‐free diet as well as in rats fed a diet supplemented with 0.4% Cr, by sampling from an artery and from the hepatic and portal veins. Arterial [GAA] was 5.61 μM and 2.22 μM, respectively, in the rats fed the Cr‐free and Cr‐supplemented diet. We found a significant uptake of GAA across the livers of the rats fed the Cr‐free diet but no significant uptake in those fed the Cr‐supplemented diet. There was no significant difference in GAMT activity between the two diet groups. Supported by CIHR.