Catalysts general acid-base

In acid-base catalysis there is at least one step in the reaction mechanism that consists of a generalized acid-base reaction (a proton transfer between the catalyst and the substrate). The protonated or deprotonated reactant species or intermediate then reacts further, either with... 

It appears that all these possibilities can be excluded. If reactions (a) or (gf) were rate-limiting the reaction velocity would be independent of the concentration of the substrate, while reaction (e) (identical with (Z)) would predict no catalysis by acids or bases. If reactions (b), (d) or (h) determined the rate the reaction would show specific catalysis by hydrogen or hydroxide ions, in place of the general acid-base catalysis actually observed. Reactions (c), (f) and (m) are unacceptable as rate-limiting processes, since they involve simple proton transfers to and from oxygen. Reactions (j) and (k) might well be slow, but their rates would depend upon the nucleophilic reactivity of the catalyst towards carbon rather than on its basic strength towards a proton as shown in Section IV,D it is the latter quantity which correlates closely with the observed rates. 

The reactions are accompanied by a considerable volume change, and a dilatometric method was employed by Bell and Higginson (1949), who added acetaldehyde-water mixtures (containing about equal quantities of MeCHO and MeCH(OH)2) to an excess of acetone, and thus measured kj, in presence of a large number of acid catalysts. The direct hydration of acetaldehyde in aqueous buffer solutions is inconveniently fast at room temperatures, but ( (j + A ) was measured dilatometrically at 0°C by Bell and Darwent (1950), who established the existence of general acid-base catalysis. 

Abstract The last few years have seen a considerable increase in our understanding of catalysis by naturally occurring RNA molecules, called ribozymes. The biological functions of RNA molecules depend upon their adoption of appropriate three-dimensional structures. The structure of RNA has a very important electrostatic component, which results from the presence of charged phosphodiester bonds. Metal ions are usually required to stabilize the folded structures and/or catalysis. Some ribozymes utilize metal ions as catalysts while others use the metal ions to maintain appropriate three-dimensional structures. In the latter case, the correct folding of the RNA structures can perturb the pKa values of the nucleo-tide(s) within a catalytic pocket such that they act as general acid/base catalysts. The various types of ribozyme exploit different cleavage mechanisms, which depend upon the architecture of the individual ribozyme. 

Fig. 4A The mechanism of cleavage by ribonuclease A. Two imidazole residues function as general acid-base catalysts. B The single-metal-ion mechanism proposed for cleavage by the hammerhead ribozyme. One metal ion binds directly to the pro-Rp oxygen and functions as a general base catalyst. C The double-metal-ion mechanism proposed for cleavage by the hammerhead ribozyme. Two metal ions bind directly to the 2 -oxygen and the 5 -oxygen...

Jencks (1972) has concluded that concerted bifunctional acid-base catalysis is rare or nonexistent because of the improbability of meeting simultaneously at two sites on reactant and catalyst the conditions of the rule which he has proposed for concerted reactions. The rule states that concerted general acid-base catalysis of complex reactions in aqueous solution can occur only (a) at sites that undergo a large change in pAT in the course of the reaction, and (b) when this change in pAf converts 2m unfavourable to a favourable proton transfer with respect to the catalyst, i.e., the pAT-value of the catalyst is intermediate between the initial and final pAf-vadues of the substrate site. 

Yeast enolase (Mr 93,316) is a dimer with 436 amino acid residues per subunit. The enolase reaction illustrates one type of metal ion catalysis and provides an additional example of general acid-base catalysis and transition-state stabilization. The reaction occurs in two steps (Fig. 6-23a). First, Lys345 acts as a general base catalyst,... 

There is no tyrosine residue corresponding to Tyr-248. Instead, a histidine residue, His-231, is suitably located to be a general-acid-base catalyst in the reaction. 

In the case of beef liver catalase, distal histidine (His74) is believed to serve as a general acid-base catalyst to facilitate the heterolytic 0—0 bond of hydroperoxide bound to the heme (Scheme 2) (21). The Asnl47 residue located near the heme could assist the heterolysis by making the distal site into a polar atmosphere. The same acid-base mechanism has been attributed to peroxidases... 

While most of peroxidases utilize the distal histidine as a general acid-base catalyst, chloroperoxidese (CPO) uniquely uses glutamate as the terminal acid-base catalyst (Scheme 8) (56). 

The presence of a general acid/base catalyst at the creatine binding site, together with a recent measurement of a short (y 6 A) distance from Cr +ADP to the phosphorus of P-creatine (13), imply an associative mechanism for the creatine kinase reaction. 

Li, Y. K., Chir, J., Tanaka, S. and Chen, F. Y. (2002). Identification of the general acid/base catalyst of a family 3 /Lglucosidasc from FlcNobacterium meningosepticum, Biochemistry 41, 2751-2759. 

The catalytic mechanism of cysteine proteinases is broadly similar to that of serine proteinases, in that there is an acyl-enzyme intermediate (Fersht, 1985, p. 414) and a histidine residue which is considered to act as a general acid-base catalyst however the balance of evidence appears to favour the mechanism shown in Scheme 18 in which, in contrast to that for the serine... 

It is therefore understandable that the aminotriazole- or BrCN-modified enzyme no longer participates in ligand interchange reactions, particularly if, as implied, YH acts as a general acid-base catalyst. That HA rather than Ar is the reactive species may therefore indicate that the distal site, embedded in a hydrophobic environment, is largely inaccessible to anions and cations. 

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