Vitamin B12 and folate are supplied via two major pathways, the conversion of homocysteine to methionine and the conversion of methyl malonyl coenzyme A to succinyl coenzyme A. Therefore, the defect in both the vitamins results in an increase in both serum homocysteine and methylmalonic acid. Hence, homocysteine, vitamin B12, and folate are closely linked together in the so-called one-carbon cycle, making vitamin B12 the necessary co-enzyme for the methyl donation from 5-methyl-tetra-hydrofolate in tetra-hydro-folate, necessary for methionine synthetase. Folate is a cofactor in one-carbon metabolism, and it promotes the remethylation of homocysteine, which can cause DNA strand breakage, oxidative stress and apoptosis. Vitamin B12 and folate are involved in nucleic acid synthesis and in the methylation reactions, and their deficit causes the inhibition of S-adenosylmethionine mediated methylation reactions, and through the related toxic effects of homocysteine, a possible direct alteration of the vascular endothelium and inhibition of N-methyl-D-Aspartate receptors take place. We discussed the possible and still controversial role of homocysteine accumulation in cerebral pathologies, starting from vascular events to neurodegeneration and to endothelium damage mechanism.

Homocysteine in neurology: From endothelium to Neurodegeneration

MORETTI, Rita;DAL BEN, MATTEO;TIRIBELLI, CLAUDIO
2017-01-01

Abstract

Vitamin B12 and folate are supplied via two major pathways, the conversion of homocysteine to methionine and the conversion of methyl malonyl coenzyme A to succinyl coenzyme A. Therefore, the defect in both the vitamins results in an increase in both serum homocysteine and methylmalonic acid. Hence, homocysteine, vitamin B12, and folate are closely linked together in the so-called one-carbon cycle, making vitamin B12 the necessary co-enzyme for the methyl donation from 5-methyl-tetra-hydrofolate in tetra-hydro-folate, necessary for methionine synthetase. Folate is a cofactor in one-carbon metabolism, and it promotes the remethylation of homocysteine, which can cause DNA strand breakage, oxidative stress and apoptosis. Vitamin B12 and folate are involved in nucleic acid synthesis and in the methylation reactions, and their deficit causes the inhibition of S-adenosylmethionine mediated methylation reactions, and through the related toxic effects of homocysteine, a possible direct alteration of the vascular endothelium and inhibition of N-methyl-D-Aspartate receptors take place. We discussed the possible and still controversial role of homocysteine accumulation in cerebral pathologies, starting from vascular events to neurodegeneration and to endothelium damage mechanism.
2017
feb-2017
Pubblicato
File in questo prodotto:
File Dimensione Formato  
Homocysteine in Neurology From Endothelium to Neurodegeneration.pdf

Accesso chiuso

Descrizione: articolo principale
Tipologia: Documento in Versione Editoriale
Licenza: Digital Rights Management non definito
Dimensione 2.22 MB
Formato Adobe PDF
2.22 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2907551
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 8
social impact