Molecular mechanisms of homocysteine toxicity

• Published in: Biochemistry (Moscow) Vol. 74; no. 6; pp. 589 - 598
• Main Author: Boldyrev, A. A
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : SP MAIK Nauka/Interperiodica 01-06-2009; SP MAIK Nauka/Interperiodica; Springer Nature B.V
• Subjects: Amino acids; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Blood Cells - drug effects; Cardiovascular Diseases - etiology; Carnosine - pharmacology; Carnosine - physiology; Female; Homocysteine - analogs & derivatives; Homocysteine - blood; Homocysteine - metabolism; Homocysteine - toxicity; Humans; Hyperhomocysteinemia - embryology; Hyperhomocysteinemia - genetics; Hyperhomocysteinemia - metabolism; Life Sciences; Male; Microbiology; Molecular biology; Neurodegenerative Diseases - etiology; Neurology; Neurons - drug effects; Peptides; Pregnancy; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - metabolism; Review; Risk Factors; Toxicity; homocysteine; homocysteic acid; lymphocytes; NMDA receptors; neurons; neutrophils
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297909060017

Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.