Effect of dietary supplementation with folate on choline deficiency-induced hyperhomocysteinemia in rats

The effects of dietary supplementation with folate (20 mg/kg diet), 2.5% serine, or both on choline deprivation-induced hyperhomocysteinemia were investigated in rats fed a 10% casein diet (10C) or 25% soybean protein diet (25S) to determine whether folate supplementation with or without serine can suppress choline deficiency-induced hyperhomocysteinemia. Choline deprivation-induced enhancement of plasma homocysteine concentration was significantly suppressed by supplementation with folate, serine, or both, but the effects of these supplements were partial or limited in the rats fed both 10C and 25S. The extents of suppression of plasma homocysteine increments by folate, serine, or both were 29.6, 37.8, and 46.2%, respectively, in rats fed 10C and 27.2, 36.6, and 42.8%, respectively, in rats fed 25S. There was no significant additive effect between folate and serine, a source of C1 units. Folate supplementation with or without serine significantly increased or tended to increase hepatic 5-methyltetrahydrofolate concentration together with methionine synthase (MS) and cystathionine β-synthase (CBS) activities and MS mRNA level in both rats fed 10C and rats fed 25S. Hepatic betaine-homocysteine S-methyltransferase activity was unaffected by folate with or without serine. Supplementation with serine alone significantly increased hepatic serine concentration and increased or tended to increase CBS activity slightly. It is thought that the suppressive effect of folate on choline deficiency-induced hyperhomocysteinemia was due to increased metabolism of homocysteine via the MS pathway and that the suppressive effect of serine was due to increased metabolism of homocysteine via cystathionine formation. One of the reasons for the insufficient effect of folate alone or in combination with serine is thought to be that the capacity of the MS pathway for homocysteine metabolism is less enhanced by supplementation with folate and serine.