Cobalamin-folate interrelations.
Cobalamin deficiency leads to impaired folate function as demonstrated by markedly impaired single-carbon unit transfer into purine, thymidine and methionine. This occurs in the total absence of 'methylH4folate trapping'. In cobalamin deficiency there is impaired synthesis of formylH4folate and raised levels of endogenous formate in blood and liver. FormylH4folate and methionine reverse the effects of cobalamin deficiency. Methionine provides formate via its metabolism to methylthioribose. Recently it has been suggested that the neuropathy of cobalamin deficiency is due to impaired methylation but this was not confirmed. It is likely that defects demonstrated in marrow and liver are also the explanation for the effects of cobalamin deficiency in the CNS.
Chanarin
I
I
Section of Haematology, Northwick Park Hospital, Harrow, Middlesex, UK.
Deacon
R
R
Lumb
M
M
Perry
J
J
D000749:Anemia, Megaloblastic / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002493:Central Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D003067:Coenzymes / Q000502:physiology; D005492:Folic Acid / Q000502:physiology*; D005494:Folic Acid Deficiency / Q000150:complications / Q000378:metabolism; D005561:Formates / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000096:biosynthesis; D008954:Models, Biological; D013763:Tetrahydrofolates / Q000096:biosynthesis; D013936:Thymidine / Q000096:biosynthesis; D014805:Vitamin B 12 / Q000502:physiology*; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000378:metabolism
D003067:Coenzymes; D005561:Formates; D013763:Tetrahydrofolates; C030544:formic acid; D005492:Folic Acid; D008715:Methionine; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate; D013936:Thymidine