Folate and homocysteine metabolisms and their roles in the biochemical basis of neuropsychiatry

Abstract

This work aims to study recent climatic oscillations and their influence on sedimentation in the Ria de Vigo, a coastal embayment in Galicia, NW Spain. It is based on the study of clay mineral assemblages, in conjunction with other proxies (granulometric, geochemical, geochronological and microfaunal), in the core KSGX 24. A Benthic Foraminifera High Productivity (BFHP) proxy was used to determine changes in the flux of organic matter (OM) at the bottom of the study area. Total organic carbon (TOC) content is not a suitable proxy to estimate changes in the past supply of OM due to diagenetic processes. The sedimentation was finest in 3 sections: ~ 230-214 cm, ~ 185-73 cm and ~ 20-0 cm. These muddy sections are characterised, in general, by higher proportions of detrital minerals, concentrations of several chemical elements related to lithogenic sources and BFHP values. In addition, these sections are impoverished in carbonates, Ca, Sr and La when compared with the layers with the highest sand content. The clay mineral assemblage of the studied site, characterised by the dominance of illite, intermediate concentrations of kaolinite and minor amounts of smectite and chlorite, reveals the prevalence of a typical temperate humid climate in the last 3 ka BP, the estimated age for the core base. However, the quantities of illite and chlorite increase in the muddy layers. The characteristics of these muddy layers were interpreted as representing relatively cold climatic oscillations associated with the strengthening of northerly winds and the prevalence of an upwelling regime corresponding to well-known periods, such as the first cold period of the Upper Holocene (~ 2.9 ka cal BP), the Dark Ages (between ~ 2.2 -1.2 ka cal BP) and the Little Ice Age (~ 0.6 ka cal BP).

Functional AdoMet Isosteres Resistant to Classical AdoMet Degradation Pathways

“…5–15 Consistent with this, alterations in methylation-dependent processes are associated with cancer, 16 neurodegenerative/neuropsychiatric disorders, 17–19 inflammation, 20,21 metabolic disorders, 22 fundamental development/regenerative medicine, 23,24 susceptibility to disease/adverse drug response, 25,26 and drug resistance. 13–15,27,28 While there have been great advances in methylation-dependent bioinformatics and disease-associated biomarkers, 29–31 the study of intracellular MT spatial/temporal resolution, specificity, and/or function remains a challenge.…”

Genetics and epigenetics of autism: A Review

“…HCy is also important for the synthesis of some amino acids and polypeptides, such as cystathionine, cysteine, and glutathione. Some neuropsychiatric disorders have been related to abnormalities of the one‐carbon metabolic pathway . One proposed mechanism is that autistic children have lower levels of glutathione, while having elevated levels of HCy and S‐adenosylhomocysteine, which are indicative of oxidative stress, and a poorer ability to eliminate heavy metal, such as mercury …”

“…Some neuropsychiatric disorders have been related to abnormalities of the one-carbon metabolic pathway. 121 One proposed mechanism is that autistic children have lower levels of glutathione, while having elevated levels of HCy and S-adenosylhomocysteine, which are indicative of oxidative stress, and a poorer ability to eliminate heavy metal, such as mercury. 122 Since a study of 35 ASD children and age-and sex-matched controls showed that the dietary choline and betaine as well as their plasma choline and betaine levels were lower than that of controls, 123 it was thought that it could be possible to supplement these children with choline and betaine for alleviating their high HCy levels.…”

The Role of Folate Dependent Genetic Susceptibility in The Risk of Multiple Sclerosis

“…However, the most important disease group, which is associated with FA deficiency and hyperhomocysteinemia, is neurological and psychiatric diseases. In recent years, there have been a number of publications that FA is associated with diseases such as Parkinson's, MS, Alzheimer, stroke, anxiety disorders, depression, schizophrenia, bipolar disorder, congenital neural tube defects [14][15][16]. High levels of Hcy are toxic to neural cells therefore Hcy contributes to the pathogenesis of neurodegenerative disorders.…”