Proximal base effect

Models of Hemoprotein Active Sites (b) Proximal base effect... 

In dicyanocobalt(III) a,b,c,d,e,g-hexamethyl-f-stearylamide cobyrinate (derivative 3) the six peripheral amide groups of vitamin B12 have been replaced with methyl ester groups, and the proximal base of the vitamin at the f-position with a stearylamide group (11). Electrodes prepared with this ionophore and DOS as the plasticizer were also selective for thiocyanate and nitrite over the rest of the anions tested. The main anionic interferent was salicylate. In all cases, the response of the electrodes to the preferred anions was sub-Nemstian. Overall, the selectivity pattern obtained with ionophore 3 is similar to that of 2 and to that of the hydrophobic cobyrinate-based electrodes reported previously (5, 12, 13). This observation suggests that in all cobyrinate ionophores the anions interact with the cobalt(III) center, and that the side chains of the corrin ring have a small effect on the selectivity of this interaction. 

Because protein conformational changes are changes in geometry, it has been tempting to consider a steric effect as the controlling factor in heme reactivity. This effect, as proposed by Hoard and Perutz (6, 7), involves a tension imposed by the protein on the proximal base, which in turn either pulls on the center of the heme as if it were a pump diaphragm or fits the naturally domed shape of the deoxyheme. Re-... 

Comparisons between R- and T-state hemoglobins on the one hand and a variety of synthetic model compounds on the other have allowed an evaluation of the possible occurrence and importance of electronic, proximal-base tension, and distal-side steric effects on the kinetics of ligation of CO and 02. Although all of these effects could influence the reactivities of hemoproteins, we conclude that hemoglobin reactivity and cooperativity are controlled predominantly by the presence or absence of proximal-base tension. 

There are several processes that account for the enhancement of reaction rates by enzymes. The major mechanisms are proximity-entropy effects, substrate strain, covalent catalysis, and acid-base catalysis. 

In many cases, a combination of mechanisms will exist, proximity-entropy effects, covalent modification, and general acid-base effects as well as other processes that we may not have discussed. 

Electronic and Polar Effects. Electron-donating groups on the porphyrin ring or on the proximal base increase... 

Proximal and Distal Steric Effects. Similar to Hb, R and T states can be induced in heme models by intentional choice of proximal bases. If 1-MeIm is replaced with 2-MeIm or 1,2-diMeIm, the planar heme... 

Steric (tension) and electronic effect from proximal base B... 

An alternative explanation of the effect of the proximal base in determining R and T behaviour relies on strong hydrogen-bonding to the N-1 proton of imidazole which in effect causes deprotonation. Deprotonation of the imidazole base does have an effect on the binding rate of CO on Fe TPP complexes in toluene but this is in the opposite sense to what might be expected. It is unlikely that this mechanism is operative but the effect could be explained by relatively small changes in the state of protonation. 

The significance of the proximity effect on conductor impedance is well-known. There are a number of papers that derive a theoretical formula of impedance and admittance [23, 24, 25, 26, 27, 28-29] and discuss impedance variation due to proximity based on numerical simulations [30, 31, 32-33]. The proximity effect may be very important in a steady-state power system s performance from a power loss viewpoint some quantitative results at a frequency of 50 or 60 Hz have been published [34, 35, 36-37]. 

Constraint control strategies can be classified as steady-state or dynamic. In the steady-state approach, the process dynamics are assumed to be much faster than the frequency with which the constraint control appHcation makes its control adjustments. The variables characterizing the proximity to the constraints, called the constraint variables, are usually monitored on a more frequent basis than actual control actions are made. A steady-state constraint appHcation increases (or decreases) a manipulated variable by a fixed amount, the value of which is determined to be safe based on an analysis of the proximity to relevant constraints. Once the appHcation has taken the control action toward or away from the constraint, it waits for the effect of the control action to work through the lower control levels and the process before taking another control step. Usually these steady-state constraint controls are implemented to move away from the active constraint at a faster rate than they do toward the constraint. The main advantage of the steady-state approach is that it is predictable and relatively straightforward to implement. Its major drawback is that, because it does not account for the dynamics of the constraint and manipulated variables, a conservative estimate must be taken in how close and how quickly the operation is moved toward the active constraints. 

The thia2ides are actively secreted into the proximal tubules, where they exert their action on the luminal side of the tubules. The diuretic effect occurs within 1 h after oral adininistration, and the duration of action varies from 4 to 24 h depending on which thia2ide-type diuretic is used. The diuretic effects of the thia2ides are not influenced by acid—base conditions of the blood or urine. Probenecid, which also is secreted into the proximal tubules, may block the diuretic effects of the thia2ides. 

Up to Harvest. Oilseed rape and field beans are used as break crops for winter wheat on a variety of soils, and potatoes are used on the lighter soils. Sugar beet may also be grown, but this depends not only on the soil but also on the proximity of a sugar beet processing factor. Four Rothamsted-based experiments compared the effectiveness of winter wheat and winter oilseed rape in their use of labelled nitrogen fertilizer. Potatoes were included in two of these experiments and sugar beet and field beans in one experiment each. Two criteria based on the... 

Figure 28.13(a) Skin effect in isolated rectangular busbars, (neglecting the proximity effect) (Courtesy l ndian Aluminium Co, based Alcon of Canada)... 

Drawing inferences from the literature available on the subject (see the further reading at the end of the chapter), based on laboratory tests, practical experience and the field data available, deratings for different configurations are shown in Table 28.7 which should be sufficient to account for the likely proximity effects... 

AC ratings are based on spacings at which the proximity effect is considered almost negligible (> 500 mm Section 28.8). 

Clearly, proximity and orientation play a role in enzyme catalysis, but there is a problem with each of the above comparisons. In both cases, it is impossible to separate true proximity and orientation effects from the effects of entropy loss when molecules are brought together (described the Section 16.4). The actual rate accelerations afforded by proximity and orientation effects in Figures 16.14 and 16.15, respectively, are much smaller than the values given in these figures. Simple theories based on probability and nearest-neighbor models, for example, predict that proximity effects may actually provide rate increases of only 5- to 10-fold. For any real case of enzymatic catalysis, it is nonetheless important to remember that proximity and orientation effects are significant. 

A third class of sequence elements can either increase or decrease the rate of transcription initiation of eukaryotic genes. These elements are called either enhancers or repressors (or silencers), depending on which effect they have. They have been found in a variety of locations both upstream and downstream of the transcription start site and even within the transcribed portions of some genes. In contrast to proximal and upstream promoter elements, enhancers and silencers can exert their effects when located hundreds or even thousands of bases away from transcription units located on the same chromosome. Surprisingly, enhancers and silencers can function in an orientation-independent fashion. Literally hundreds of these elements have been described. In some cases, the sequence requirements for binding are rigidly constrained in others, considerable sequence variation is... 

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