8-ALA-S activity

Adult rats Chronic Pb exposure Levels of ALA and activities of 8-ALA-D and 8-ALA-S with Pb exposure Activities of 8-ALA-D in kidney, liver, and spleen reduced but not in brain 8-ALA-S activity increased in spleen and reduced in liver Silbergeld and Lamon (1982)... 

Adult female rabbits Oral Pb dosing 17 pM Pb acetate for 5 days Levels of 8-ALA-D and 8-ALA-S activity versus PbB in various tissues 8-ALA-D activity reduced in blood, bone marrow, and liver 8-ALA-S activity unchanged in liver and bone marrow Zareba and Chmielnicka (1992)... 

The stimulation of 6-ALA-S activity in response to Pb inhibition at steps downstream in heme biosynthesis, particularly Pb inhibition of 8-ALA-D,... 

Figure 6.46 LC-NMR chromatogram at 500 MHz from system described in Figure 6.45. Each NMR spectmm represents 12 coadded scans acquired in 12 s. Flow rate, 5 pFmin active volume, 1.11. No solvent suppression scheme was used, and all spectra were acquired with the spectrometer gain set to maximum, (a) Injected amounts 2.3 (26 nmol) 4.8 (20 nmol), and 4.8 pg (21 nmol) of Ala, Gly-Tyr and Phe-Ala (I, II, III), respectively, (b) injected amounts 8 nmol of each component. Extracted NMR spectra shown in (c) Ala, (I), (d) Gly-Tyr (II), (e) Phe-Ala (III). Reproduced from [85] with permission. Copyright 1999 American Chemical Society.

Wild-type subtilisin BPN with the mutation Ser — Cys-24 has a kcat value of 59 s 1 and a KM value of 200 fxM with the synthetic substrate N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, compared with a rate constant of 1.1 X 10 8 s 1 for its spontaneous hydrolysis under the same conditions. Replacement of Asp-32, His-64, and Ser-221 one at a time by alanine reduced the value of kcat by factors of 3 X 104, 2 X 106, and 2 X 106, respectively. Converting all three to alanine also decreases activity by 2 X 106. The value of KM increases only by a factor of two on all these mutations.34 It is unlikely that the residual activity results from the presence of a small amount of wild-type active site in the thiol mutants... 

Resistance to vancomycin in enterococci is due to modification of the D-Ala-D-Ala binding site of the peptidoglycan building block in which the terminal D-Ala is replaced by D-lactate. This results in the loss of a critical hydrogen bond that facilitates high-affinity binding of vancomycin to its target and loss of activity. This mechanism is also present in vancomycin-resistant S aureus strains (MIC s32. ug/mL), which have acquired the enterococcal resistance determinants. The mechanism for reduced vancomycin susceptibility of vancomycin-intermediate strains (MICs = 8-16 g/mL) is not known. 

Further changes in the P1-P5 region, which resulted in improved efficacy for these synthetic substrates, were based on elastin, HLE s natural substrate [36]. This excellent substrate is an insoluble, structural protein, which is primarily composed of hydrophobic amino acid residues. However, it also contains a number of Lys-derived, cross-linked residues, such as desmosine and isodesmosine, that incorporate a positively charged pyridinium ring. In order to model this cross-linking feature, Lys or various amino-protected forms of Lys, were systematically incorporated into the substrate MeO-8uc-Ala-Ala-Pro-Val-NA (4-1). Replacement of any single residue with Lys led to decreased activity, for example, (4-2)-(4-4) Table 2.4). However, the use of side-chain protected Lys derivatives (e.g. the NHj terminus protected with benzyloxycarbonyl or picolinyl) led to increased reactivity to elastase with the optimal position for substitution being P4, see (4-5)-(4-8). 

Hepatocytes were treated as described in Table III, and activities of 8-aminolevulinate synthetase (ALAS), ferrochelatase, and heme oxygenase were determined as described previously (Kim et aL, 1995). NMMA, N -monomethyl-L-arginine SNAP, S-nitrosoacetylpenacillamine. 

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