The pathogenesis of homocysteinemia: Interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine

Jacob Selhub, Joshua W. Miller

Research output: Contribution to journalArticle

446 Scopus citations

Abstract

A unified, biochemical hypothesis is proposed to explain the pathogenesis of homocysteinemia. This hypothesis is based on the existence of coordinate regulation by S-adenosylmethionine (SAM) of the partitioning of homocysteine between de novo methionine synthesis and catabolism through cystathionine synthesis. This coordination, which serves to modulate the cellular concentration of homocysteine based on the requirements for methionine, is impaired in homocysteinemia. This hypothesis is evaluated in the context of the conditions known to be associated with homocysteinemia, including enzymatic defects and vitamin deficiencies. The novelty of the hypothesis is the assertion that impairment of one homocysteine metabolic pathway must lead to the impairment of the other homocysteine metabolic pathway to cause homocysteinemia. This extends the simplistic view that a block of only one of the pathways is sufficient to cause homocysteinemia.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume55
Issue number1
StatePublished - Jan 1992
Externally publishedYes

Keywords

  • Cystathionine β-synthase
  • Folate
  • Homocysteine
  • Homocysteinemia
  • Methylenetetrahydrofolate reductase
  • S-adenosylmethionine
  • Vascular disease
  • Vitamin B-12
  • Vitamin B-6

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Fingerprint Dive into the research topics of 'The pathogenesis of homocysteinemia: Interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine'. Together they form a unique fingerprint.

Cite this