Moderate folate deficiency influences polyamine synthesis in rats.
Spermidine, spermine and putrescine are polyamines, essential growth factors in mammalian cells. Decarboxylated S-adenosylmethionine (SAM) is an essential precursor in the formation of both spermidine and spermine. SAM is formed from methionine through the addition of adenosine. Because 5-methyltetrahydrofolate donates a methyl group to homocysteine to produce methionine, folate deficiency may decrease polyamine synthesis. Weanling male Sprague-Dawley rats were fed an amino acid-defined diet with 2 mg folic acid/kg diet (control) or no added folic acid (test). Blood, liver, brain, jejunum, ileum and colon samples were collected at the end of 5 wk. Compared with controls, rats fed the test diet had a 72% reduction in plasma folate (123.6 +/- 13.1 vs. 34.6 +/- 2.2 nmol/L, P < 0.001) and a 42% reduction in RBC folate (2834.4 +/- 218.3 vs. 1651.8 +/- 75.9 nmol/L, P < 0.001). Hepatic spermidine and spermine in folate-depleted rats were 58 (P < 0.001) and 67% (P < 0.01) higher, respectively, than in controls. Plasma putrescine was 27% higher (P < 0.05) than in controls. The polyamine concentrations of the jejunum, ileum, colon and brain did not differ. This study suggests that mild folate deficiency influences polyamine synthesis, but contrary to our hypothesis, hepatic spermidine and spermine were increased, as was circulating putrescine. This may have occurred for a number of reasons including increased enzyme activity or overcompensation by the betaine-homocysteine transmethylation pathway in the liver. Further study is necessary to clarify interactions between folate and polyamine metabolism and to determine whether polyamines are involved in the damaging effects of folate deficiency.
Sun
Dongmei
D
Division of Nutrition and Dietetics, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada S7N 5C9.
Wollin
Armin
A
Stephen
Alison M
AM
D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis* / Q000097:blood; D001921:Brain / Q000378:metabolism; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011700:Putrescine / Q000096:biosynthesis / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000378:metabolism; D013095:Spermidine / Q000096:biosynthesis / Q000097:blood; D013096:Spermine / Q000096:biosynthesis / Q000097:blood
D015317:Biogenic Polyamines; D013096:Spermine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D013095:Spermidine; D011700:Putrescine