Homocysteine, folate deficiency, marker

A vitamin B12 coenzyme is needed to convert methyknalonyl coenzyme A to succinyl co-enzyme A. Patients with vitamin B12 deficiency almost always have increased urinary excretion of methylmalonic acid (MMA). MMA is amore specific marker for vitamin B12 deficiency compared to homocysteine. MMA levels are not elevated in folate deficiency, as folate does not participate in MMA metabolism. Levels of both MMA and homocysteine are usually elevated prior to the development of hematologic abnormalities and reductions in serum vitamin B12 levels. MMA levels need to be interpreted cau-... 

In vitamin B12 deficiency, methionine synthase is inhibited causing increased levels of homocysteine and SAH. SAH in turn inhibits SAM mediated methylation, thereby leading to toxic levels of homocysteine causing direct damage to the vascular endothelium and inhibition of iV-methyl-o-aspartate receptors (NMDA) (Moretti et al. 2008). Homocysteine is produced entirely from the methylation cycle, as it is totally absent from any dietary source (Pietrzik and Bronstrup 1997). Hence, an elevated plasma homocysteine concentration is a sensitive marker for vitamin B12 and folate deficiency (Pametti et al. 1997). In addition, it can be due to increased frequency of impaired genetic capacity to metabolize homocysteine (Nilsson et al. 1996). 

Several analytes are known to be indicative of folate metabolism. Plasma total homocysteine increases when there is a deficiency of 5-MTHF, such that the methylation of homocysteine to methionine is compromised. However, though plasma homocysteine is considered to be a sensitive functional indicator, it is not specific because its concentration can be influenced by deficiency of other vitamins (Bg and B12) involved in the metabolism of homocysteine. Similarly the methylation of DNA is dependent upon adequate 5-MTHF. A sensitive new method for the rapid detection of abnormal methylation patterns in global DNA patterns has been reported and may have promise as a functional marker, as may the measurement of the degree of uracil incorporation into DNA, 5,10-metliylene THF being required for die conversion of deoxyuridine monophosphate (dUMP) to dTMP by thymidylate synthetase. ... 

Nilsson, K., Gustafson, L., and Hultberg, B. 1999. Plasma homocysteine is a sensitive marker for tissue deficiency of both cobalamines and folates in a psychogeriatric population. Dementia and Geriatric Cognitive Disorders. 10 476-482. 

In cooperation with vitamin B12, folic acid methylates homocysteine to methionine. Therefore, homocysteine is a suitable marker for the supply of folate. In the case of a deficiency, the serum concentration of this marker is clearly raised compared with the normal value of 8-lOpmol/ml, resulting in negative effects on health because higher concentrations of homocysteine are toxic. 

---