Folates

Abstract

This chapter will deal with analytical procedures for 5-methyltetrahydrofolic acid (5MTHF) in cerebrospinalfluid (CSF) and serum. Folic acid is a water-soluble vitamin that functions as a one-carbon donor in various metabolic cycles. It is involved in the biosynthesis of thymidylates and purines, methionine synthesis via homocysteine remethylation, the methylation of phospholipids, the interconversion of serine and glycine, and the metabolism of histidine and formate.It is therefore essential for growth, reproduction, and maintenance of normal body function. The natural form is referred to as folate; it consists mainly of 5MTHF and 10-formyltetrahydrofolate in their polyglutamate derivatives [1]. 5MTHF is the active one-carbon donor. It is transported through the blood–brain barrier to serve for a number of reactions in the centralnervous system.
Serum folate deficiency is known to be associated with megaloblastic anemia, high blood levels of homocysteine, and neural tube defect in newborns as a result of folate shortage of the mother[2, 3]. Cerebral folate deficiency (CFD) is a recently recognized neurological disorder found in several children with psychomotor retardation, spastic paraplegia, cerebellar ataxia, and dyskinesia.These patients have very low 5MTHF in their CSF, normal blood folates [4, 5], and some patients display a high titer of folate receptor-blocking autoantibodies[6].
CFD is further associated with the following inherited metabolic disorders: 5,10-methylen-tetrahydrofolate reductase (MTHFR) deficiency [7], 3-phosphoglycerate dehydrogenase (PGDH) deficiency [8], dihydropteridine reductase (DHPR) deficiency [9], as well as with Rett syndrome [10], and Aicardi-Goutières Syndrome [11]. Furthermore, folate deficiency may be associated with congenital folate malabsorption, severe malnutrition, and formiminotransferase deficiency.
5MTHF was initially measured by microbiological and radioisotope dilution as-say [12, 13], and later by high-pressure liquid chromatography (HPLC) using electrochemical (EC), ultraviolet, or fluorescence detection [14-16]. Compared to other methods, EC detection is more sensitive.