Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects

This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its “direct” derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects

Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine.

Item does not contain fulltextIn order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed. The earliest was directed medially; these cells invaginated into a median groove and were the main contributors to the initial neural tube closure. Once the median groove was completed, cells changed direction and moved anteriorly to contribute to the anterior neural plate and head fold. This plate developed into the anterior neuropore, which started to close from the 4-somite stage onwards by convergence of its neural folds. Posteriorly, from the initial closure site onwards, the posterior neuropore started to close almost instantaneously by convergence of its neural folds. Homocysteine is adversely involved in human neural tube closure defects. After application of a single dose of homocysteine to chick embryos, a closure delay at the initial closure site and at the neuropores, flattening of the head fold and neural tube, and a halt of cell movements was seen. A possible interference of Hcy with actin microfilaments is discussed