The International Journal of Biochemistry & Cell Biology
Related papers: molecules in focusHomocysteine
Introduction
Homocysteine (2-amino-4-mercaptobutyric acid) was synthesized in 1932 by duVigneaud who was studying the sulfur of insulin. In his biography he states, “…the entire homocystine work leading to the studies of transulfuration (sic) and transmethylation would not have taken place if we had been able to account for the sulfur of insulin at the beginning and if the absence of methionine in insulin had been known at that time. The paths which research may take are indeed curious.” [1].
Section snippets
Structure
Fig. 1 illustrates the structure of homocysteine, a thiol formed by the demethylation of methionine. Animal tissues contain some free thiol but most of the compound occurs as homocystine, the disulfide of homocysteine; homocysteine–cysteine mixed disulfide, and homocysteine bound to protein by disulfide bonds.
The pathways
Homocysteine represents a point of intersection of two pathways — the methionine cycle and the transsulfuration sequence (Fig. 2) [2]. The methionine cycle is formed by the synthesis of S-adenosylmethionine (AdoMet); the numerous specific transmethylation reactions that yield S-adenosylhomocysteine (AdoHcy) as a product; the reversible adenosylhomocysteinase reaction that favors synthesis of AdoHcy unless the products — adenosine and homocysteine — are removed; and the remethylation of
Biological functions
The four biological functions of homocysteine, implicit in Fig. 2, are (1) as a precursor for cystathionine, cysteine and further metabolites; (2) as a means for methionine conservation; (3) as a methyl receptor in the betaine–homocysteine methyltransferase reaction, an obligatory step in choline catabolism; and (4) as a substrate that is essential for the recycling of tissue folates. Since methionine synthase is the only reaction that utilizes methyltetrahydrofolate, folates will be “trapped”
Medical applications
The clinical relevance of homocyst(e)ine became apparent in 1962 with the first descriptions of patients with “Homocystinuria” due to a homozygous defect in cystathionine synthase [8]. Thrombovascular events dominated the clinical picture. When these also occurred in patients with homocystinuria due to failure of remethylation (defects in cobalamin metabolism or methylenetetrahydrofolate reductase deficiency), the link between homocysteine and vascular disorders was established. Patients with
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Homocysteine – A predictor for five year-mortality in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia
2023, Experimental GerontologyCitation Excerpt :Homocysteine is a non-proteinogenic amino acid, which is not a constituent of our diet, but part of the methionine cycle (Moretti and Caruso, 2019). The metabolism of homocysteine forms the interface between two different pathways, one leading back to methionine and the other to cystathionine (Finkelstein and Martin, 2000; Selhub, 1999). Apart from its important metabolic role, increased homocysteine can also be harmful.