Enzymes decreasing prediction

Consensus sites for phosphorylation were evident in the neuronal NOS enzyme from the predicted protein sequences derived from cDNA analysis. In vitro biochemical studies indicate that nNOS can be phosphorylated by calcium/calmodulin-dependent protein kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, and protein kinase C. Phosphorylation of nNOS by all of these enzymes decreases NOS catalytic activity in vitro (Dawson and Snyder, 1994 Bredt etal., 1992 Dinerman etal., 1994a). Calcineurin, a protein phosphatase, dephosphorylates NOS and subsequently increases its catalytic activity (T. M. Dawson etal., 1993). Multiple levels of constitutive nNOS regulation are thus possible by phosphorylation. 

Relationships between reaction rate and temperature can thus be used to detect non-classical behaviour in enzymes. Non-classical values of the preexponential factor ratio (H D i 1) and difference in apparent activation energy (>5.4kJmoRi) have been the criteria used to demonstrate hydrogen tunnelling in the enzymes mentioned above. A major prediction from this static barrier (transition state theory-like) plot is that tunnelling becomes more prominent as the apparent activation energy decreases. This holds for the enzymes listed above, but the correlation breaks down for enzymes... 

At low temperatures, the nonenzymatic reaction is reduced to a larger extent than the enzymatic reaction. The mass transfer rate is reduced to a smaller extent. Mass transfer limitation is required for high enantiomeric excess and determines the conversion rate. Therefore, the volumetric productivity decreases at lower temperatures. The equilibrium constant is considerably higher at low temperatures, resulting in a higher extent of conversion or a lower HCN requirement. Both the volumetric productivity and the required enzyme concentration increase by increasing the reaction temperature and aqueous-phase volume while meeting the required conversion and enantiomeric excess [44]. The influence of the reaction medium (solvent and water activity) is much more difficult to rationalize and predict [45],... 

Notably, natural variation in the type III PKS active site cavity, like that observed in Ipomoea and Petunia, does not result in functionally impaired enzymes, but in fact, generates catalytically active enzymes that display both altered substrate and product specificities. Sequential increases in the side chain volume of position 256 in alfalfa CHS2 result in decreases in polyketide chain length and predictable shifts in the ratio of tetraketide to triketide reaction products.32 These results functionally link the volume of the elongation/cyclization lobe in type III PKS to chain length determination. 

There appear to be gender differences in the pharmacokinetics of selective benzodiazepines such as chlordiazepoxide and diazepam. As would be predicted from studies evaluating the effect of OCs on various P450 enzymes, the levels of hydroxylated and demethylated benzodiazepines are increased in OC users, and the levels of conjugated benzodiazepines are decreased in OC users. Importantly, however, the pharmacokinetic effect may not always predict the impairment on psychomotor and cognitive tasks seen in women who are concurrently given OCs and benzodiazepines. 

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