Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is currently known about the substrate binding site of the human UDP-glucuronosyltransferases (UGTs) and the structural elements that affect their complex substrate selectivity. In order to further understand and extend our earlier findings with phenylalanines 90 and 93 of UGT1A10, we have replaced each of them with Gly, Ala, Val, Leu, Ile or Tyr, and tested the activity of the resulting 12 mutants toward eight different substrates. Apart from scopoletin glucuronidation, the F90 mutants other than F90L were nearly inactive, while the F93 mutants' activity was strongly substrate dependent. Hence, F93L displayed high entacapone and 1-naphthol glucuronidation rates, whereas F93G, which was nearly inactive in entacapone glucuronidation, was highly active toward estradiol, estriol and even ethinylestradiol, a synthetic estrogen that is a poor substrate for the wild-type UGT1A10. Kinetic analyses of 4-nitrophenol, estradiol and ethinylestradiol glucuronidation by the mutants that catalyzed the respective reactions at considerable rates, revealed increased K(m) values for 4-nitrophenol and estradiol in all the mutants, whilst the K(m) values of F93G and F93A for ethinylestradiol were lower than in control UGT1A10. Based on the activity results and a new molecular model of UGT1A10, it is suggested that both F90 and F93 are located in a surface helix at the far end of the substrate binding site. Nevertheless, only F93 directly affects the selectivity of UGT1A10 toward large and rigid estrogens, particularly those with substitutions at the D ring. The effects of F93 mutations on the glucuronidation of smaller or less rigid substrates are indirect, however.
Steroids 2011 Dec 11
PMID:Phenylalanine 93 of the human UGT1A10 plays a major role in the interactions of the enzyme with estrogens. 2184 74

Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis, showed strong anti-lung cancer and anti-hepatocarcinoma activities. In this research, a gas chromatography/mass spectrometry (GC/MS) method was developed and validated for the metabolic profiling of RPS intervention in H22 hepatocarcinoma mice. Data were analyzed with partial least-squares discrimination analysis (PLS-DA). As a result, RPS displayed different pathway to decrease energy production of the mice. For the normal mice, RPS significantly decreased the concentration of lipid, glycerate, succinate and lactate, but increased glucose and valine levels. All these indicated that RPS inhibited glucose and valine to transform ketones which participated in the ATP production. For the H22 cancer mice, RPS increased the concentration of lipid and glycerate, but significantly decreased glucose, glycine and alanine levels in the serum. This phenomenon indicated that RPS inhibited the oxidation of fatty acids pathway and the gluconeogenesis pathway which participated in the energy supply for the body. RPS also inhibited glycine and alanine production to block the tumor growth. This selective effect of RPS to different condition of mice would improve understanding of the antitumor pathway of RPS involved in H22 hepatocarcinoma mice.
Steroids 2014 Jun
PMID:Antitumor pathway of Rhizoma Paridis Saponins based on the metabolic regulatory network alterations in H22 hepatocarcinoma mice. 2464 33

Microwave (MW) assisted chemical reactions are currently gaining considerable importance in organic synthesis to contribute in green technology. Considering the importance of peptidomimetic steroid-amino acid conjugates - a novel class of hybrid compounds having diverse biological properties, we report here synthesis of these compounds of alanine and valine methyl esters with seco-steroids (A, B and D ring cleavage) in expedited way by MW promoted Ugi-four-component reaction (Ugi-4CR).
Steroids 2015 Jun
PMID:Microwave (MW) irradiated Ugi four-component reaction (Ugi-4CR): Expedited synthesis of steroid-amino acid conjugates--A novel class of hybrid compounds. 2570 Oct 96


<< Previous 1 2