An inborn error of metabolism associated with mutations in the human methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene has been identified. The proband presented with SCID, megaloblastic anemia, and neurologic abnormalities, but the causal metabolic impairment is unknown. SCID has been associated with impaired purine nucleotide metabolism, whereas megaloblastic anemia has been associated ...

FAUST is a software tool that generates formal abstractions of (possibly non-deterministic) discrete-time Markov processes (dtMP) defined over uncountable (continuous) state spaces. A dtMP model is specified in MATLAB and abstracted as a finite-state Markov chain or a Markov decision process. The abstraction procedure runs in MATLAB and employs parallel computations and fast manipulations based...

Clinical vitamin B12 deficiency can result in megaloblastic anemia, which results from the inhibition of DNA synthesis by trapping folate cofactors in the form of 5-methyltetrahydrofolate (5-methylTHF) and subsequent inhibition of de novo thymidylate (dTMP) biosynthesis. In the cytosol, vitamin B12 functions in the remethylation of homocysteine to methionine, which regenerates THF from 5-methyl...

The large-scale extraction and partial purification of endogenous 3',5'-cyclic UMP, 3',5'-cyclic IMP and 3',5'-cyclic dTMP are described. Rat liver, kidney, heart, spleen and lung tissues were subjected to a sequential purification procedure involving freeze-clamping, perchlorate extraction, alumina and Sephadex ion-exchange chromatography and preparative electrophoresis. The samples thus obtai...

Intact mitochondria of Neurospora crassa incorporate deoxythymidine 5'-monophosphate (dTMP) into deoxyribonucleic acid but not the label from (methyl-3H) deoxythymidine. Mitochondrial homogenates contain deoxythymidylate kinase (EC 2.7.4.9), deoxycytidylate aminohydrolase (dCMP deaminase) (EC 3.5.4.12), and thymidylate synthetase (EC 2.1.1b), but not thymidine kinase (EC 2.7.1.21) activity. dTM...

Arsenic exposure increases risk for cancers and is teratogenic in animal models. Here we demonstrate that small ubiquitin-like modifier (SUMO)- and folate-dependent nuclear de novo thymidylate (dTMP) biosynthesis is a sensitive target of arsenic trioxide (As2O3), leading to uracil misincorporation into DNA and genome instability. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and serine hyd...

background: owing to its favourable decay characteristics 177lu [t1/2= 6.71 d, eβ(max)= 497 kev] is an attractive radionuclide for various therapeutic applications. ethylene diamine tatramethylene phosphonate (edtmp) is one of the most widely used ligands which form stable complexes with various radionuclides and all the complexes. materials and methods: enriched 176lu2o3 was dissolved in 0.1 n...

A new flexible ultramicroporous solid, La(H(5)DTMP)·7H(2)O (1), has been crystallized at room temperature using the tetraphosphonic acid H(8)DTMP, hexamethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid). Its crystal structure, solved by synchrotron powder X-ray diffraction, is characterised by a 3D pillared open-framework containing 1D channels filled with water. Upon dehydration, a n...