Abstract
Homocysteine (Hcy) is a sulfur-containing non-proteinogenic amino acid derived in methionine metabolism. The increased level of Hcy in plasma, hyperhomocysteinemia, is considered to be an independent risk factor for cardio and cerebrovascular diseases. However, it is still not clear if Hcy is a marker or a causative agent of diseases. More and more research data suggest that Hcy is an important indicator for overall health status. This review represents the current understanding of molecular mechanism of Hcy metabolism and its link to hyperhomocysteinemia-related pathologies in humans. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated protein, nucleic acid and carbohydrate oxidation and lipoperoxidation, products known to be involved in cytotoxicity. Additionally, we examine the role of Hcy in thiolation of proteins, which results in their molecular and functional modifications. We also highlight the relationship between the imbalance in Hcy metabolism and pathogenesis of diseases, such as cardiovascular diseases, neurological and psychiatric disorders, chronic kidney disease, bone tissue damages, gastrointestinal disorders, cancer, and congenital defects.
Highlights
It has been reported that the ratio between SAM/SAH should be used as a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis [74]. Another scientific group investigate the effect of elevated Hcy level on fatty acid binding protein 4 (FABP4) [75]. Their results showed that FABP4 has a very important function in lipid metabolism disturbance after Hcy treatment and that DNA methyltransferase 1 (DNMT1; EC 2.1.1.37) could be a potential therapeutic target in Hcy-related atherosclerosis [75]
The imbalance in Hcy metabolism is linked with a number of human pathologies
It remains unclear whether excessive Hcy concentration directly contributes to the pathogenesis of diseases or it represents a biomarker of metabolic aberrations, such as aberrant methyl group metabolism
Summary
Homocysteine (Hcy) is a non-essential, sulfur-containing, non-proteinogenic amino acid. The other excessively important enzymatic activity of transsulfuration enzymes (CBS, CSE) is H2 S production from catalysis of Hcy and/or Cys. H2 S is the third gasotransmitter and is produced in different cells and tissues in human body. The central nervous system lacks BHMT, being dependent on folate/vitamin B12-dependent pathway for the conversion of Hcy to Met, which refers brain to higher vulnerability to the increased Hcy levels [16]. Supplementation with natural folate-rich foods, folic acid and folate, vitamins B6 or B12 and the intake of proteins rich in Met and Cys) [22] These dietary nutrients influence the supply of methyl groups and regulate the biochemical pathways for methylation processes. Hcy may act together with the other cellular changes associated with aging in development of cellular dysfunction
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