Effects of choline deficiency and methotrexate treatment upon rat liver.

  title={Effects of choline deficiency and methotrexate treatment upon rat liver.},
  author={Elizabeth Anne Pomfret and Kerry Ann daCosta and Steven H. Zeisel},
  journal={The Journal of nutritional biochemistry},
  volume={1 10},
Effects of choline deficiency and methotrexate treatment upon liver folate content and distribution.
The effects of feeding rats a choline deficient diet, of treating rats with low doses of methotrexate, and of combined choline deficiency and MTX treatment upon the content and distribution of folates in liver were examined.
Choline deficiency and methotrexate treatment induces marked but reversible changes in hepatic folate concentrations, serum homocysteine and DNA methylation rates in rats.
It is suggested that CD and MTX treatment appear to impair the capacity of tissues to incorporate folate in only 2 weeks and affect other biomarkers of one-carbon metabolism such as Hcy concentration and DNA methylation.
Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.
The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase
Methotrexate alters carbon flow through the hepatic folate-dependent one-carbon pool in rats.
The tracer kinetic experiments quantitatively demonstrate the extent to which methotrexate alters the actual carbon flow through the hepatic folate-dependent one-carbon pool, primarily directed at diminishing the reductive carbon flow towards methyltetrahydrofolate and methionine synthesis.
Diethanolamine induces hepatic choline deficiency in mice.
It is demonstrated that DEA treatment causes a spectrum of biochemical changes consistent with choline deficiency in mice and a clear dose concordance between DEA-induced choline deficiencies and hepatocarcinogenic outcome is demonstrated.
Choline deprivation induces hyperhomocysteinemia in rats fed low methionine diets.
The results indicate that choline deprivation can easily induce prominent hyperhomocysteinemia when rats are fed relatively low methionine diets such as a standard soybean protein diet and low casein diet, possibly through the suppression of homocysteine removal by both remethylation and cystathionine formation.
MTX does not affect enhanced biosynthesis and metabolism of S-adenosylmethionine in testosterone-induced hypertrophic mouse kidney.
One of the anabolic effects of testosterone, apart from its profound induction of ornithine decarboxylase, which results in the stimulation of putrescine biosynthesis, is the enhancement of synthesis and levels of S-adenosylmethionine (AdoMet), and an increase in cellular methylation intensity.
Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans.
A strong association in premenopausal women of the 5,10-methylenetetrahydrofolate dehydrogenase-1958A gene allele polymorphism with 15 times increased susceptibility to developing organ dysfunction on a low-choline diet is found.
Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline.
The results show that PEMT normally supplies a significant portion of the daily choline requirement in the mouse and, when this pathway is knocked out, mice are unable to attain normal concentrations of all choline metabolites even with a supplemental source of dietary choline.


Methotrexate effects on hepatic betaine levels in choline-supplemented and choline-deficient rats.
The data suggest that the betaine lowering seen in livers of choline-fed rats may be due to utilization as a means of compensating for the MTX-induced loss of N5 methyltetrahydrofolate for the vital methylation of homocysteine in methionine biosynthesis.
Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver.
Choline deficiency can deplete hepatic stores of AdoMet under dietary conditions that only minimally decrease the availability of methionine within liver.
The effect of methotrexate on homocysteine methylating agents in rat liver.
It is suggested that betaine may compensate for N5 methyltetrahydrofolate as a methylating substance when folate metabolism is antagonized in rat liver.
Choline antagonism of methotrexate liver toxicity in the rat.
The data strongly suggest that, in the rat model, methotrexate produced liver toxicity by virtue of an effect other than inhibition of DNA synthesis; and that this toxicity can be blocked without impairing metotrexate effect on bone marrow by the administration of choline, a lipotropic agent requiring methylation for its synthesis.
The effects of choline deficiency and choline re-feeding upon the metabolism of plasma and liver lipids.
  • D. Haines
  • Biology, Medicine
    Canadian journal of biochemistry
  • 1966
The findings confirm that the fatty liver of choline deficiency is the result of an impairment in the transport of triglyceride from the liver, and support the hypothesis that it occurs because of a restriction in the synthesis of phosphatidyl choline which is required for lipoprotein formatio...
Changes in plasma methionine and total homocysteine levels in patients receiving methotrexate infusions.
Investigation of the effects of moderate dose to very high dose methotrexate on methionine and total homocysteine as reflections of metotrexate induced intracellular events found changes in homocy steine and methionines may reflect biological effects of methot Rexate that may predict cytotoxicity of metHotrexate.
Effect of dietary methyl group deficiency on folate metabolism in rats.
Increased use of folate for methyl group biosynthesis may be responsible for the loss of folates from the liver in rats fed the methyl-deficient diet.
The influence of dietary choline intake upon liver ethanolamine metabolism.
The effect of dietary choline upon liver ethanolamine metabolism was investigated by measurement of the changes in the liver levels of phospholipids and their precursors and in the metabolism of