Disease relevance of SRM

• Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells [1].
• Methylthiopropylamine, a potent inhibitor of spermidine synthase and its antiproliferative effect on human lymphoid leukemia Molt 4B cells [2].
• Using a synthetic deoxyoligonucleotide mixture constructed for a tryptic peptide of the bovine enzyme as a probe, cDNA coding for the full-length subunit of spermidine synthase was isolated from a human decidual cDNA library constructed on phage lambda gt11 [3].
• Only 7% of cohort women worked in the high exposure locations in the plant, compared with 39.6% of men, and no increased risk of cancer mortality was observed among women; but breast cancer mortality was raised (SRM = 2.15) [4].
• The tumors of patients with and without metastases at the time of resection of the primary tumor contained different (P = 0.0314) concentrations of cells with histochemically demonstrable alpha-naphthylbutyrate esterase in SCM but not in SRM [5].

Psychiatry related information on SRM

• Lifestyle regularity as measured by the SRM related to age, morningness, subjective sleep quality and time-of-day variations in alertness, but not to gender, extroversion or neuroticism [6].
• VO(2) and power output (SRM), aerobic and anaerobic energy contributions, and VO(2) kinetics (mean response time to 63% of the VO(2) observed at 2 km) were determined throughout each TT [7].
• Pattern (PRM) and spatial recognition (SRM), spatial span (SSP), spatial working memory (SWM), and paired associate learning (PAL) from Cambridge Neuropsychological Test Automated Battery were performed twice [8].
• Because of its rigor and specificity, the components of the SRM may serve as a heuristic for thinking about interpersonal feedback in group therapy [9].
• To summarize, SRM induces a state of relaxation as observed by psychological tests and by effects such as increases in the surface temperature of the hands [10].

High impact information on SRM

• Specific inhibition of spermidine synthase from mycobacteria by ethambutol [11].
• Spermidine synthase (putrescine aminopropyltransferase, PAPT) catalyzes the biosynthesis of spermidine, a ubiquitous polyamine [12].
• The AdoDATO binding site is lined with residues conserved in PAPT enzymes from bacteria to humans, suggesting a universal catalytic mechanism [12].
• The crystal structure of the PAPT from Thermotoga maritima (TmPAPT) has been solved to 1.5 A resolution in the presence and absence of AdoDATO (S-adenosyl-1,8-diamino-3-thiooctane), a compound containing both substrate and product moieties [12].
• A number of transgenic mouse lines carrying human ornithine decarboxylase, spermidine synthase and S-adenosylmethionine decarboxylase gene have been generated [13].

Chemical compound and disease context of SRM

• Spermidine synthase from sensitive bacteria was inhibited by more than 90% by 50 microM-dicyclohexylamine in vitro, and the concentration of spermidine was decreased in E. coli and Ps. aeruginosa by 70% and in Strep. uberis by 95%, whereas in Strep. agalactiae 5 mM-dicyclohexylamine did not affect the concentration of spermidine at all [14].
• Molecular, biochemical and genetic characterization of ornithine decarboxylase, S -adenosylmethionine decarboxylase and spermidine synthase establishes that these polyamine-biosynthetic enzymes are essential for growth and survival of the agents that cause African sleeping sickness, Chagas' disease, leishmaniasis and malaria [15].

Biological context of SRM

• Mathematical/Statistical modeling of the data from time-course and concentration-effect experiments of gene expression from nine polyamine pathway genes represented on the HGU95Av2 chip, indicates that three biosynthetic pathway genes (SAMDC, ODC1 and SRM) are down-regulated and one catabolic pathway gene (SSAT) is up-regulated [16].
• Mapping of the human spermidine synthase gene (SRM) to 1p36 and a probable pseudogene (SRML2) to region 3p14-->q21 [17].
• Regulation of the human spermidine synthase mRNA translation by its 5'-untranslated region [18].
• The identity of the isolated cDNA was confirmed by comparison of the deduced amino acid sequence with resolved sequences of the tryptic peptides of bovine spermidine synthase [3].
• The human spermidine synthase (EC 2.5.1.16) gene was isolated from a genomic library constructed with DNA obtained from a human immunoglobulin G (IgG) myeloma cell line [19].

Anatomical context of SRM

• The inhibition of spermidine synthase gene expression by TGF-beta 1 protein was also observed in other hepatoma cell lines [1].
• Spermidine synthase was purified to apparent homogeneity from human spleens (8700-fold) by affinity chromatography [20].
• An increased mRNA content of spermidine synthase was found in phytohemagglutinin stimulated human peripheral lymphocytes and in cultured human myeloma (Sultan) cells stimulated to grow by change of the culture medium [18].
• In the present study the effect of the 5'-untranslated region of spermidine synthase mRNA on the post-transcriptional control of its expression was studied both in vitro in rabbit reticulocyte system and in cultured mammalian cells [18].
• Polymerase chain reaction analysis with DNA obtained from human x hamster somatic cell hybrids indicated that human spermidine synthase genomic sequences segregate with human chromosome 1 [19].

Associations of SRM with chemical compounds

• We found a gene that was down-regulated by TGF-beta 1 to be completely identical in an approx. 620 bp segment to the gene for the enzyme spermidine synthase, which mediates the conversion of putrescine into spermidine [1].
• The ODC, ADOMETDC, and SPDSYN overproducer strains exhibited a high level of resistance to difluoromethylornithine, 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine, and n-butylamine, respectively, confirming previous observations that these agents specifically target polyamine enzymes [21].
• 1. 2-Fluoroputrescine has a high affinity for spermidine synthase (Km 12 microM) and obeys normal Michaelis-Menten kinetics [22].
• 3. 2,2-Difluoroputrescine has even a higher affinity for spermidine synthase than putrescine and 2-fluoroputrescine; however, at concentrations greater than 25 microM one observes inhibition of the aminopropylation reaction [22].
• In this work, the standard reference materials NIST SRM 613, Trace Elements in 1 mm Glass Wafers, and NIST SRM 1577a, Trace Elements in Bovine Liver, are examined at the 10100-ng mass level using X-ray beams of 5-150 microm in diameter [23].

Other interactions of SRM

• Three certified reference materials (NIST SRM 1570a spinach leaves, NIST SRM 1573a tomato leaves and BCR CRM 679 white cabbage) were selected for this study, the goal always being to develop a fast procedure that could be robust enough to provide a satisfactory performance for all of them, without any modifications in the conditions applied [24].
• For this purpose we determined hTERT mRNA concentration and telomerase activity in human normal (RPE-28) and cancer (A549) cell lines as well as in human serum (SRM 1951A) [25].
• The reliability of the method was proved by analyzing PAH spiked water (simulated rain) and using NIST SRM 1649 ('urban dust') as certified material for particle-bound PAHs in precipitation [26].
• To check the method, SRM Lyphochek Urine Metal control--Biorad, Seronorm Trace Elements--Nycomed and GWB Human Hair (China) were used [27].
• Methythioadenosine phosphorylase (MTAP) functions solely in the polyamine pathway of mammals to remove the methylthioadenosine (MTA) product from both spermidine synthase (2.5.1.16) and spermine synthase (2.5.1.22) [28].

Analytical, diagnostic and therapeutic context of SRM

• Mouse antisera against spermidine synthase revealed only one band, of Mr 35,000, in all purified enzyme preparations and in crude human tissue extracts in immunoblotting [20].
• Using Southern blot analysis of panels of human podent somatic cell hybrids and chromosomal in situ hybridization, we have been able to assign human spermidine synthase DNA sequences to 1p36 (SRM) and 3p14-->q21 (SRML2) [17].
• The sample extracts were each analyzed within 1.2 min using a positive ion turbo-ionspray selected reaction monitoring liquid chromatography/mass spectrometric (SRM LC/MS) method in which 768 samples were easily analyzed within 22 h (maximum of 820 samples in 24 h) [29].
• SRM 2392 includes DNA from two lymphoblast cell cultures (CHR and 9947A) and cloned DNA from the CHR HV1 region, which contains a C stretch and is difficult to sequence [30].
• The results demonstrate that the developed HPLC/ES-SRM methods are powerful approaches for the identification of organoarsenic species in crude sample extracts [31].

References