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101.
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103.
Smith TK Crossman A Paterson MJ Borissow CN Brimacombe JS Ferguson MA 《The Journal of biological chemistry》2002,277(40):37147-37153
A series of synthetic analogues of d-GlcN alpha 1-6-d-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol, consisting of 22 variants of the d-GlcN or lipid components, were tested in trypanosomal and human (HeLa) cell-free systems. The assays measured the abilities of the analogues to act as substrates or inhibitors of the enzymes of glycosylphosphatidylinositol biosynthesis downstream of GlcNAc-phosphatidylinositol (GlcNAc-PI) de-N-acetylase. One compound, 4-deoxy-d-GlcN alpha 1-6-d-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol, proved to be an inhibitor of both the trypanosomal and HeLa pathways, whereas 4-O-methyl-d-GlcN alpha 1-6-d-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol and the 4'-epimer, d-GalN-alpha1-6-d-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol, were neither substrates nor inhibitors. The results with other analogues showed that the 6-OH of the alpha-d-GlcN residue is not required for substrate recognition in the trypanosomal and human pathways, whereas the 3-OH group is essential for both. Parasite-specific recognition of the beta-linked analogue d-GlcN beta 1-6-d-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol is striking. This suggests that, like the GlcNAc-PI de-N-acetylase, the trypanosomal glycosylphosphatidylinositol alpha-mannosyltransferases, inositol acyltransferse and ethanolamine phosphate transferase, do not recognize the 2-, 3-, 4-, and 5-OH groups of the d-myo-inositol residue, whereas the human inositol acyltransferase and/or first alpha-mannosyltransferase recognizes one or more of these groups. All of the various lipid analogues tested served as substrates in both the trypanosomal and HeLa cell-free systems, suggesting that a precise lipid structure and stereochemistry are not essential for substrate recognition. However, an analogue containing a single C18:0 alkyl chain in place of sn-1,2-dipalmitoylglycerol proved to be a better substrate in the trypanosomal than in the HeLa cell-free system. These findings should have a bearing on the design of future generations of specific inhibitors of the trypanosomal glycosylphosphatidylinositol biosynthetic pathway. 相似文献
104.
Ganesh Kumar Veeramachaneni K Kranthi Raj Leela Madhuri Chalasani Sai Krishna Annamraju Bondili JS Venkateswara Rao Talluri 《Bioinformation》2015,11(12):535-542
Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world
population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among
the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico
methods like structure based virtual screening, QikProp, docking studies and binding energy calculations three molecules namely
zinc85531017, zinc95919096 and zinc33963788 from the natural database were reported as the potential inhibitors for the pancreatic
lipase. Among them zinc95919096 presented all the interactions matching to both standard and crystal ligand and hence it can be
further proceeded to drug discovery process. 相似文献
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108.
R Martin DS Buchan JS Baker J Young N Sculthorpe FM Grace 《Biology of sport / Institute of Sport》2015,32(4):307-313
The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO2max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P < 0.01) with non-significant trends for fasting insulin (P= 0.08), and HOMA-IR (P=0.06). CRF decreased (P < 0.01) in SPE such that POST intervention CRF was significantly lower (P< 0.05) in SPE. Fasting plasma glucose (P < 0.01), insulin (P< 0.01) and HOMA-IR (P< 0.01) increased significantly amongst SPE. The main finding of the present study is that 7-weeks of SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term. 相似文献
109.
The cDNA cloning and molecular evolution of reptile and pigeon lactate dehydrogenase isozymes 总被引:1,自引:0,他引:1
The cDNAs encoding lactate dehydrogenase isozymes LDH-A (muscle) and LDH-B
(heart) from alligator and turtle and LDH-A, LDH-B, and LDH-C (testis) from
pigeon were cloned and sequenced. The evolutionary relationships among
vertebrate LDH isozymes were analyzed. Contrary to the traditional belief
that the turtle lineage branched off before the divergence between the
lizard/alligator and bird lineages, the turtle lineage was found to be
clustered with either the alligator lineage or the alligator-bird clade,
while the lizard lineage was found to have branched off before the
divergence between the alligator/turtle and bird lineages. The pigeon
testicular LDH-C isozyme was evidently duplicated from LDH-B (heart), so it
is not orthologous to the mammalian testicular LDH-C isozymes.
相似文献
110.
Sacha AFT van Hijum Richard JS Baerends Aldert L Zomer Harma A Karsens Victoria Martin-Requena Oswaldo Trelles Jan Kok Oscar P Kuipers 《BMC bioinformatics》2008,9(1):1-10