The metabolism of homocysteine: pathways and regulation

  title={The metabolism of homocysteine: pathways and regulation},
  author={James D. Finkelstein},
  journal={European Journal of Pediatrics},
  • J. Finkelstein
  • Published 24 March 1998
  • Biology, Medicine
  • European Journal of Pediatrics
Abstract Two pathways, the methionine cycle and transsulfuration, account for virtually all methionine metabolism in mammals. Every tissue possesses the methionine cycle. Therefore, each can synthesize AdoMet, employ it for transmethylation, hydrolyze AdoHcy, and remethylate homocysteine. Transsulfuration, which occurs only in liver, kidney, small intestine and pancreas, is the means for catabolizing homocysteine. Liver has a unique isoenzyme of MAT that allows the utilization of excess… 
Folate and homocysteine metabolisms and their roles in the biochemical basis of neuropsychiatry.
This review aims to summarize both one-carbon metabolism and its relationships with neuropsychiatric disorders.
SUMMARY Homocysteine, a metabolite of the methionine cycle, is a strong independent risk factor for cardiovascular disease. Although the methionine in dietary protein can transiently affect levels of
The Role of Cystathionine β-Synthase in Homocysteine Metabolism
Cystathionine β-synthase (CBS) is the first enzyme in the transsulfuration pathway, catalyzing the conversion of serine and homocysteine to cystathionine and water. The enzyme contains three
Biochemistry and Metabolism
Homocysteine, a metabolite of the methionine cycle, is a strong independent risk factor for cardiovascular disease. Although the methionine in dietary protein can transiently affect levels of total
Homocysteine in the Pathogenesis of Chronic Glaucoma
1.1 Metabolic pathway Methionine is one of four amino acids that form succinyl CoA. This sulphur containing amino acid is the source of homocysteine (Hcy). It is converted to S-adenosylmethionine
Methionine-deficient diet induces post-transcriptional downregulation of cystathionine β-synthase.
The results imply that methionine deprivation induces a metabolic state in which methamphetamineionine is effectively conserved in tissue by shutdown of the transsulfuration pathway by an S-adenosylmethionine-independent mechanism that signals a rapid downregulation of CBS protein.
Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview
Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease and a link has been postulated between homocysteine, or its intermediates, and an alterated DNA methylation pattern.
S-adenosyl-L-homocysteine hydrolase and methylation disorders: Yeast as a model system
The advantages of yeast as an experimental system to understand pathologies associated with AdoHcy accumulation will be discussed and the strong product inhibitor S-adenosyl-L-homocysteine hydrolase is discussed.
Hormonal Regulation of Cystathionine β-Synthase Expression in Liver*
Results show that insulin has a direct role in regulating homocysteine metabolism by regulating the hepatic transsulfuration pathway.
Effects of moderate hyperhomocysteinaemia induced by 4 weeks methionine-enriched diet on metabolite profile and mesenteric artery function in rats
A 2-fold elevation of plasma homocysteine did not impair mesenteric artery vasodilatation during 4 weeks of a methionine-rich diet, and asymmetrical dimethylarginine and adenosine, which have been shown to be changed in more severe degrees of hyperhomocysteinaemia, remained unaltered.


Regulation of methionine metabolism: Effects of nitrous oxide and excess dietary methionine☆
Methionine is an essential amino acid that is also converted to S-adenosylmethionine, which is used by methyltransferases that methylate DNA, RNA, protein, lipid, etc., and form
The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine.
The novelty of the hypothesis is the assertion that impairment of one homocysteine metabolic pathway must lead to the impairment of the otherhomocysteines metabolic pathway to cause homocysteinemia, which extends the simplistic view that a block of only one of the pathways is sufficient to cause Homocysteemia.
Methionine metabolism in mammals: regulatory effects of S-adenosylhomocysteine.
By altering the distribution of homocysteine between these competing pathways, S -adenosylhomocy steine may be significant in the regulation of methionine metabolism in the intact animal.
Homocysteine catabolism: levels of 3 enzymes in cultured human vascular endothelium and their relevance to vascular disease.
It is suggested that persons who are deficient in cystathionine beta-synthase or 5-methyltetrahydrofolate:homocysteine methyltransferase activity may not only develop homocysteinemia, but also have vascular endothelium which is more susceptible to damage by homocysteines than persons with normal enzyme levels.
Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat.
This study demonstrates the complete absence of any activity for this enzyme in the brain of the three species examined, and demonstrates that the enzyme exists only in the cytoplasm of rat liver cells.
[1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing.
Two loci are quantitatively important regulatory points in Met conservation in vivo: 1) the distribution of Met between the pathways of protein anabolism and TM (Met locus) and 2) the Distribution of homocysteine between RM and TS (homocystein locus).
Transsulfuration depends on heme in addition to pyridoxal 5'-phosphate. Cystathionine beta-synthase is a heme protein.
It is suggested that heme is functionally incorporated into CBS only during protein folding, and the first instance of an enzyme that depends upon both heme and PLP for its function is described.
Methionine metabolism in mammals.
  • J. Finkelstein
  • Chemistry, Medicine
    The Journal of nutritional biochemistry
  • 1990
Article de synthese sur le metabolisme de la methionine, acide amine essentiel, chez les mammiferes, de la regulation du metabolisme (mise en evidence and importance relative of chaque facteur).
Plasma Homocysteine and Cardiovascular Disease
Within a few years after the first cases of cystathionine fj-synthase deficiency were discovered, additional patients and their susceptibility to life-threatening vascular disease were described, and the interest in homocysteine was greatly enhanced by the discovery of the inborn errors, homocystinuria.
Determination of in vivo protein binding of homocysteine and its relation to free homocysteine in the liver and other tissues of the rat.
The half-lives of Hcy are such that participation of both free and bound Hcy in metabolic regulation is feasible, and the turnover rates of S-adenosylhomocysteine and Hcy to be production rate limited and the dissociation rate of the Hcy-protein complex may greatly exceed the turnover rate of H Cy.