Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.5.7.1 (
methylenetetrahydrofolate reductase
)
2,116
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The putative gene of Plasmodium vivax serine hydroxymethyltransferase (PvSHMT; EC 2.1.2.1) was cloned and expressed in Escherichia coli. The purified enzyme was shown to be a dimeric protein with a monomeric molecular mass of 49 kDa. PvSHMT has a maximum absorption peak at 422 nm with a molar absorption coefficient of 6370 M(-1) x cm(-1). The K(d) for binding of the enzyme and pyridoxal-5-phosphate was 0.14 +/- 0.01 microM. An alternative assay for measuring the tetrahydrofolate-dependent
SHMT
activity based on the coupled reaction with
5,10-methylenetetrahydrofolate reductase
(EC 1.5.1.20) from E. coli was developed. PvSHMT uses a ternary-complex mechanism with a k(cat) value of 0.98 +/- 0.06 s(-1) and K(m) values of 0.18 +/- 0.03 and 0.14 +/- 0.02 mM for L-serine and tetrahydrofolate, respectively. The optimum pH of the
SHMT
reaction was 8.0 and an Arrhenius's plot showed a transition temperature of 19 degrees C. Besides L-serine, PvSHMT forms an external aldimine complex with D-serine, L-alanine, L-threonine and glycine. PvSHMT also catalyzes the tetrahydrofolate-independent retro-aldol cleavage of 3-hydroxy amino acids. Although L-serine is a physiological substrate for
SHMT
in the tetrahydrofolate-dependent reaction, PvSHMT can also use D-serine. In the absence of tetrahydrofolate at high pH, PvSHMT forms an enzyme-quinonoid complex with D-serine, but not with L-serine, whereas
SHMT
from rabbit liver was reported to form an enzyme-quinonoid complex with L-serine. The substrate specificity difference between PvSHMT and the mammalian enzyme indicates the dissimilarity between their active sites, which could be exploited for the development of specific inhibitors against PvSHMT.
...
PMID:Serine hydroxymethyltransferase from Plasmodium vivax is different in substrate specificity from its homologues. 1954 89
We used clinical data from Iga General Hospital to examine the association between polymorphisms in
MTR
(
methionine synthase
) A2756G (rs1805087),
MTRR
(
methionine synthase reductase
) His595Tyr (rs10380),
MTHFR
(
methylenetetrahydrofolate reductase
) C677T (rs1801133),
MTHFR
A1298C (rs1801131) and
SHMT
(
serine hydroxymethyltransferase
) C1420T (rs1979277), which are genes involved in folate metabolism, and the risk of weight loss in patients with gastrointestinal cancers, with the aim of establishing personalized palliative care for each patient based on genetic information. The data from 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic for cancer chemotherapy and palliative care at Iga General Hospital from December 2011 to August 2015 were analyzed. There was no significant association between the single nucleotide polymorphisms (SNPs) in the folate metabolizing genes examined and weight loss defined as weight loss of more than 5 percent or more than 10 percent during the first 6 months after initiation of chemotherapy. We did not detect any significant association between any of the SNPs examined and overall survival of patients. The present study indicated that these SNPs have relatively limited or no roles in the genesis of cachexia in patients with gastrointestinal cancers; however, further investigations into the roles of these folate metabolizing genes in the context of cancer palliative care, from clinical, biological and epidemiological viewpoints are warranted.
...
PMID:Polymorphisms in folic acid metabolism genes do not associate with cancer cachexia in Japanese gastrointestinal patients. 3058 67
