Strong inhibition

Bimolecular E2 reactions involving OH " in aqueous solution are speeded by cationic and inhibited by anionic micelles (Minch et al., 1975) whereas spontaneous SN reactions are generally inhibited strongly by cationic micelles and less strongly by anionic micelles it is therefore relatively easy to observe micellar control of product formation. 

The electron transfer system has not been studied in detail in fish, but the metabolism of compounds such as biphenyl (37), benzo(a)pyrene (21) and 2,5-diphenyloxazole (38) by fish liver microsomes has been shown to require oxygen and NADPH generating system. The metabolism of BP (21), 2,5-diphenyloxazole (Ahokas, unpublished observation) and aldrin (27.) by fish liver microsomal enzyme system is inhibited strongly by carbon monoxide. This information and the fact that cytochrome P-1+50, as well as NADPH cytochrome c reductase system are present in fish, suggest strongly that fish have a cytochrome P-1+50 mediated monooxygenase system which is very similar to that described in mammals. 

Their rate of reaction is inhibited strongly by adding surface (therefore, an important part of the reaction mechanism must be of the free-radical type). 

With respect to five-membered lactones fused to hexopyranose units, some approaches have been reported so far and the exploitation of their synthetic potential has led to the access of new carbohydrate derivatives. Bicyclic derivatives of this type are key intermediates in the synthesis of the epimer at C-3 of the sugar moiety contained in miharamycins [212, 213]. The latter are antibiotics known to inhibit strongly Pyricularia oryzae, which produces the rice blast disease. These compounds are also considered to be a potential bioterrorism agent (Scheme 42). Hence, the 3,3-spiroepoxide 176 was converted into the 3-C-cyanomethyl derivative 177, the hydrolysis of which led to spontaneous cyclization in the presence of... 

Canaline reacts with the pyridoxal phosphate moiety of enzymes possessing this vitamin Bg-containing decarboxylases and transaminases typically are inhibited strongly by this non-protein amino acid (, ). When canaline reacts with free pyridoxal... 

Effect of NEM and pCMB Strong inhibition Strong inhibition... 

Figure 21.13. Schematic diagram of hemoglobin synthesis - - > = weak evidence of Pb inhibition —> = strong evidence of Pb inhibition. (Adapted from Natl. Acad. Sci.-Natl. Res. Counc. 1972. Airborne Lead in Perspective. Washington DC Natl. Acad. Sci.)...

Fosmidomycin 19 (Fig. 4) and its analogs are strong inhibitors of the MEP pathway, and they inhibit strongly the DXR. According to the X-ray structure of the E. coli DXR, which crystallizes in the presence of fosmidomycin, the antibiotic acts as an analog of the DXP substrate rather than as an analog of the intermediate methylerythrose phosphate (9). 

Jager (94) found. In In vitro experiments, that the atroplnase In rabbit serum was Inhibited strongly by meplperphenldol, whereas the atroplnases In rabbit and guinea pig liver were comparatively resistant to inhibition by meplperphenldol. 

Kinetics of inhibition by NSAIDs Immediate, competitive inhibition (strong for COX-1 inhibitors, weak for COX-2 inhibitors) COX-2 inhibitors noncompetitive (irreversible ), time-dependent COX-1 inhibitors competitive, immediate... 

The necessary reaction paths have now been established. The catalyst must promote oxygen insertion and mild dehydrogenation but inhibit strong oxidation and dehydrogenation. 

This brief part of our work on the reactivity of intermediates or of by-products shows why an excess of methanol is necessary for the synthesis of DMEA from [MEA,MeOH,H2]. On the one hand, it acts as a methylating agent of monoethylamine and on the other hand, it inhibits strongly the alkylation reactions i.e the MEA disproportionation into DEA and... 

Histidine None Weak inhibition Strong inhibition 85, 86, 87, 88... 

HTA is structurally related to GABA. It inhibits strongly tritium-labeled GABA binding to synaptic membranes136 and mimics some of its actions like contractions of... 

Suicide inhibitors, or mechanism-based inhibitors are modified substrates that provide the most specific means to modify an enzyme active site. The inhibitor binds to the enzyme as a substrate and is initially processed by the normal catalytic mechanism. The mechanism of catalysis then generates a chemically reactive intermediate that inactivates the enzyme through covalent modification. The fact that the enzyme participates in its own irreversible inhibition strongly suggests that the covalently modified group on the enzyme is catalytically vital. One example of such an inhibitor is N,N-dimethylpropargylamine. A flavin prosthetic group of monoamine oxidase... 

Amination of aldehydes by an amino acid aldehyde aminotransferase from Mercurialis perennis was inhibited strongly by pyruvate, oxaloacetate, and oxoglutarate, and this inhibition was suspected to be competitive (Hartmann et al., 1972). Formation of coniceine by an alanine 5-keto-octanal aminotransferase was inhibited competitively by pyruvate and uncompetitively by glyoxylate (Roberts, 1978). With the L-ornithine 2-oxoacid aminotransferase from Cucurbita pepo, severe inhibition by valine, leucine, and isoleucine could be observed, but there was no inhibition by lysine or proline (Lu and Mazelis, 1975). Cucurbita maxima ornithine aminotransferase, however, was reported to be inhibited by proline (Splittstoesser and Fowden, 1973), as well as by canavanine and diaminobutyrate. 

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