Role in enzymes

Oxidative substitutions at ring junction positions in various tetrahydro-5-deaza-pterins (79JA6068) and -flavins (77JA6721) have been studied, e.g. to give (13), and the oxidation-reduction reactions of 5-deazaflavins (e.g. 78CL1177, 80CPB3514) across the 1,5-positions, e.g. (19) (20), are involved in their co-enzymic role in enzymic oxidations (see Section... 

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. 

V. Monchois, M. Remaud-Simeon, R. R. Russell, P. Monsan, and R. M. Willemot, Characterization of Leuconostoc mesenteroides NRRL B-512F dextransucrase (DSRS) and identification of amino-acid residues playing a key role in enzyme activity, Appl. Microbiol. Biotechnol., 48 (1997) 465 -72. 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

One of the most important metals with regard to its role in enzyme chemistry is zinc. There are several significant enzymes that contain the metal, among which are carboxypeptidase A and B, alkaline phosphatase, alcohol dehydrogenase, aldolase, and carbonic anhydrase. Although most of these enzymes are involved in catalyzing biochemical reactions, carbonic anhydrase is involved in a process that is inorganic in nature. That reaction can be shown as... 

Compounds 13-18 were tested for acetylcholinesterase inhibition activity and it was found that compounds 13 and 14 exhibited acetylchohnesterase inhibition activity with IC values (inhibition of enzyme activity by 50%) of 17 and 13 pM, respectively. Compounds 15-18 showed moderate enzyme inhibition activity with ICj, values of 35, 80, 76, and 100 pM, respectively. This bioactivity data suggested that the higher enzyme inhibition potency of compounds 13 and 14 may hypothesized due to the presence of a tetrahydrofuran ring incorporated in their stractures. Fnrthermore, compounds 1 and 2 exhibited nearly the same bioactivity and this indicated that C-7 hydroxyl group does not play any role in enzyme inhibition activity. 

Hammes suggested that energy compensation has a role in enzyme-catalyzed reactions, such that there is synergism between bond cleavage and bond formation. 

Organic solvents can have a deleterious effect on enzymes, and work has been performed to gain a deeper insight into their role in enzyme inactivation, which... 

It has been pointed out in Chapter 2 (p. 39) (see also 1-4) that there is good evidence which indicates that in the hydrolysis of B-glycosides by lysozyme, the substrate must take a boat conformation in order to produce the half-chair oxocarbonium ion 0+2- -3i)- Lysozyme is therefore a good example which provides evidence that stereoelectronic effects play a key role in enzymic hydrolysis. 

Extended Arrangements of Peptides and Proteins. Amino acids are finked from the carboxyl to the amine with formation of an amide bond, often referred to as the peptide fink. The repeating (— N—C — CO—) unit is called the peptide or protein backbone. Peptides and proteins differ only in the number of amino acids present in the biopolymer chain. The cutoff is arbitrarily set. Often, but not always, a peptide is designated as having fewer than 100 amino acids and the protein possesses more. Backbone amide groups have been found to play a role in enzyme catalysis. 

Figure 16.5 Hypotheses regarding the non-equivalence of functional residues that play the same catalytic role in enzyme homologs (Todd, 2002). Each shape represents a protein structure, and each segment in the protein structure represents a position in the fold at which a functional residue can be situated. Circles denote functional residues. F and FI , etc., denote particular functions, and optF denotes the same function as F , but optimized. newF denotes a new function., N and C denote the N- and C-termini, respectively.

The element Se—not really a metal—is known to play a key role in enzymes such as the well-known glutathione peroxidase, formate dehydrogenase, glycine reductase, and the previously mentioned hydrogenases (Chapter 9). The unusual amino acid selenocysteine has a unique codon on the DNA (TGA/UGA), but selenation of serine also appears to be possible [16]. A brief review on Selenium can be found in the literature [17],... 

The observation that phosphate-free glycopeptides at low concentrations effectively inhibit the assimilation of 8-galacto-sidase by fibroblasts implies that details of the carbohydrate structure play a role in enzyme recognition by cells. The role of phosphate in the assimilation of lysosomal enzymes remains obscure. Conceivably, phosphate may lend additional specificity to the assimilation system, or perhaps it could play a role in events subsequent to the initial binding of the enzyme to the cell surface. 

Iron has roles in enzyme systems and is necessary for the synthesis of chlorophyll (Hipkins, 1983). Chlorosis, the lack of chlorophyll is the first and obvious result of iron deficiency. Chloroplasts are reduced in size and without chlorophyll. Iron deficiency also has an effect on respiration and on cell division and thus growth. An excess of phosphate, bicarbonate, Cu, Zn, Co, Cd, Mn or Ni in the growth medium may cause Fe deficiency (Hewitt, 1948, 1953 Chaney and Giordano, 1977). 

Oxygen plays an essential role in enzymic browning, but is not essential for nonenzymic browning. It may help in fact, for example, in the formation of... 

Avidin inhibits carbamyl-P synthesis by rat liver enzyme (10 units cause a 40 to 70% inhibition, depending on the purity of the enzyme), but does not affect the frog liver preparations. Preincubation of the avidin with a large excess of biotin does not prevent the inhibition of the mammalian enzyme, suggesting that the effect is not strictly due to the biotin-binding capacity of avidin. We concluded that biotin is not directly involved in the synthesis of carbamyl-P, although the enzyme may contain bound biotin. Also, this vitamin may play a role in enzyme synthesis (34). 

Apart from the cysteine backbone and carboxylate motifs, the prenyl chain also has a major role in enzyme recognition. The Cio geranyl analog of AFC (AGC) is a very poor substrate with approximately 40-fold lower substrate activity [40]. In contrast, replacement with a C20 geranylgeranyl... 

With phosphoryl chloride in alkali, imidazole gives the diphosphoryl imidazole (71) while 1-methylimidazole gives an analogous product. Such iV-phosphorylimidazoles play an important role in enzymic transphosphorylation. When two moles of imidazole (or benzimidazole) react with one mole of dialkyl (or diaryl) phosphoric acid chloride, the compounds (72) are formed, and di- and tri-imidazolides of phosphoric acid (e.g. 73) can be obtained similarly from phosphoric acid dichloride or from phosphoryl chloride (Scheme... 

Component of proteins and most enzymes Role in enzyme activation, cold resistance... 

Conformation effects of an active compound play an important role in enzyme substrate complexes. A three-membered ring between the active functional groups causes conformational rigidity. Thus cyclopropylogs of active compounds were used to study receptor geometries and to obtain information on drug activity. 

The antioxidant role of NO comes Ifom its reaction with oxygen, carbon and nitrogen centred radicals and can be seen to have a scavenger role under a range of conditions [112]. This is because of the unpaired electrons of NO which react rapidly with alkoxyl and alkyl hydroperoxyl radicals at near diffusion reaction rates (2x10 M s [113]). It is these reactions that have been suggested to have a modulatory role in enzyme- or metal-catalysed... 

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