Rate controlled synthesis

Ragulya, A.V. Rate-controlled synthesis tmd sintering of nanocrystaUme barium titanate powder. Nanostruct. Mater. 10,349-355 (1998)... 

Ordinary diffusion involves molecular mixing caused by the random motion of molecules. It is much more pronounced in gases and Hquids than in soHds. The effects of diffusion in fluids are also greatly affected by convection or turbulence. These phenomena are involved in mass-transfer processes, and therefore in separation processes (see Mass transfer Separation systems synthesis). In chemical engineering, the term diffusional unit operations normally refers to the separation processes in which mass is transferred from one phase to another, often across a fluid interface, and in which diffusion is considered to be the rate-controlling mechanism. Thus, the standard unit operations such as distillation (qv), drying (qv), and the sorption processes, as well as the less conventional separation processes, are usually classified under this heading (see Absorption Adsorption Adsorption, gas separation Adsorption, liquid separation). 

The responsiveness of a tissue to a hormone depends on the density of receptors within its component cells. The number of receptors is determined by their rate of synthesis and catabolism, which is itself controlled by complex feedback mechanisms involving hormone action. Some chemicals are known to interfere with this regulation. For example, TCDD can act to increase or decrease the expression of the oestrogen receptor. ... 

Experimental studies of this base-catalyzed condensation have revealed that it is third-order, indicating that either the second or the fourth step must be rate-determining. Studies on the intermediate I obtained by an alternative synthesis have shown that is about four times as large as k - so that about 80% of the intermediate goes on to product. These reactions are faster than the overall reaction under the same conditions, so the second step must be rate-controlling. ... 

The synthesis of methane from C02 and hydrogen was studied by Binder and White (11) over a reduced nickel catalyst (Harshaw Ni-88). The surface reaction between the C02 and hydrogen appeared to be rate controlling. The rate of reaction can be correlated by either of the following rather awkward equations ... 

Long-chain fatty acid synthesis is controlled in the short term by allosteric and covalent modification of euTymes and in the long term by changes in gene expression governing rates of synthesis of enzymes. 

Changes in the quantities of the various normal hemoglobin components during developmental stages can be explained in terms of ill-defined regulatory mechanisms which control the rate of synthesis of the polypeptide chains. Such mechanisms have to... 

Both enzymes have been continuously in the limelight of interest, as attested by thousands of reports and dozens of recent review articles on their structure and mechanism of action. Less is known about the regulation of the activity of the two enzymes under physiological conditions [2,3,35-38] and about the control of their rate of synthesis and degradation that adjusts their concentration to the physiological requirements [39-41]. 

The theoretical approach involved the derivation of a kinetic model based upon the chiral reaction mechanism proposed by Halpem (3), Brown (4) and Landis (3, 5). Major and minor manifolds were included in this reaction model. The minor manifold produces the desired enantiomer while the major manifold produces the undesired enantiomer. Since the EP in our synthesis was over 99%, the major manifold was neglected to reduce the complexity of the kinetic model. In addition, we made three modifications to the original Halpem-Brown-Landis mechanism. First, precatalyst is used instead of active catalyst in om synthesis. The conversion of precatalyst to the active catalyst is assumed to be irreversible, and a complete conversion of precatalyst to active catalyst is assumed in the kinetic model. Second, the coordination step is considered to be irreversible because the ratio of the forward to the reverse reaction rate constant is high (3). Third, the product release step is assumed to be significantly faster than the solvent insertion step hence, the product release step is not considered in our model. With these modifications the product formation rate was predicted by using the Bodenstein approximation. Three possible cases for reaction rate control were derived and experimental data were used for verification of the model. 

Pyruvate kinase (PK) is one of the three postulated rate-controlling enzymes of glycolysis. The high-energy phosphate of phosphoenolpyruvate is transferred to ADP by this enzyme, which requires for its activity both monovalent and divalent cations. Enolpyruvate formed in this reaction is converted spontaneously to the keto form of pyruvate with the synthesis of one ATP molecule. PK has four isozymes in mammals M, M2, L, and R. The M2 type, which is considered to be the prototype, is the only form detected in early fetal tissues and is expressed in many adult tissues. This form is progressively replaced by the M( type in the skeletal muscle, heart, and brain by the L type in the liver and by the R type in red blood cells during development or differentiation (M26). The M, and M2 isozymes display Michaelis-Menten kinetics with respect to phosphoenolpyruvate. The Mj isozyme is not affected by fructose-1,6-diphosphate (F-1,6-DP) and the M2 is al-losterically activated by this compound. Type L and R exhibit cooperatively in... 

Supported model catalysts are frequently prepared by thermally evaporating metal atoms onto a planar oxide surface in UHV. The morphology and growth of supported metal clusters depend on a number of factors such as substrate morphology, the deposition rate, and the surface temperature. For a controlled synthesis of supported model catalysts, it is necessary to monitor the growth kinetics of supported metal... 

In summary, certain equilibrium constants of complex formation, of solubility products and of redox potentials form a set of fixed values that must be looked at in the context of the compartment which contains the components and which controlled evolution in fair part, against a background of rising amounts of environmental oxidised elements. The other factors were the rates of synthesis as dictated by supply of energy and of reactants in the environment. 

Synthesis of glycogen from UDP-glucose is catalyzed by glycogen synthase, which is rate-controlling. As in other tissues, glycogen synthase occurs in both a phosphory-lated form, synthase-b, which depends on Glc-6-P as a positive modulator, and a dephosphorylated, independent synthase-a form, which is much more active. 

It is crucial that the flux of metabohtes through metabolic pathways be finely controlled to meet the needs of the organism at all points in time and under a variety of physiological and enviromnental conditions. Since enzymes catalyze basically aU of the reactions in metabolic pathways, it will come as no surprise to learn that control is often exerted at the level of the enzymes. There are two basic ways to do that the first way is to control the amount of an enzyme that is present, either by controlling its rate of synthesis or its rate of degradation, or both the second way is to control the activity of the enzyme. This can happen in a number of ways, frequently by interaction of an enzyme with a small molecule. 

An extremely important role of iron is the synthesis of haem for formation of erythrocytes and also for proliferating cells for synthesis of the mitochondrial enzymes that contain haem (e.g. cytochromes). The flux-generating enzyme in the synthesis of haem is aminolevulinic acid synthase (ALS) (Figure 15.20). If the cellular iron concentration is low, the concentration of this enzyme is increased in an attempt to maintain the rate of synthesis. As with the other two proteins, the concentration of ALS is controlled at the level of translation in a similar manner to that for transferrin, i.e. by increased stability of the mRNA, which is achieved by the binding of the IRP to the mRNA. 

Figure 15.20 Control of the rate of haem synthesis. The concentration of the enzyme aminolevulinic acid synthase, the first enzyme in the synthesis of haem, and the flux-generab ng enzyme, is increased by IRP. This ensures an adequate rate of synthesis of haem, even though the iron level in the cell may be low. This is achieved by stimulation of translation. Full details of the pathway are presented in Appendix 15.3.

It is an increase in the concentration of cyclins that stimulates the activity of the cycle kinases. The concentration of the cyclins is controlled by the balance between the rates of synthesis and degradation. 

As discussed above, proteases are peptide bond hydrolases and act as catalysts in this reaction. Consequently, as catalysts they also have the potential to catalyze the reverse reaction, the formation of a peptide bond. Peptide synthesis with proteases can occur via one of two routes either in an equilibrium controlled or a kinetically controlled manner 60). In the kinetically controlled process, the enzyme acts as a transferase. The protease catalyzes the transfer of an acyl group to a nucleophile. This requires an activated substrate preferably in the form of an ester and a protected P carboxyl group. This process occurs through an acyl covalent intermediate. Hence, for kineticmly controlled reactions the eii me must go through an acyl intermediate in its mechanism and thus only serine and cysteine proteases are of use. In equilibrium controlled synthesis, the enzyme serves omy to expedite the rate at which the equilibrium is reached, however, the position of the equilibrium is unaffected by the protease. 

The major routes for the synthesis and metabolism of noradrenaline in adrenergic nerves [375], together with the names of the enzymes concerned, are shown in Figure 3.1. Under normal conditions the rate controlling step in noradrenaline synthesis is the first, and the tissue noradrenaline content can be markedly lowered by inhibition of tyrosine hydroxylase [376]. Tissue noradrenaline levels can also be lowered, but to a lesser extent, by inhibition of dopamine-(3-oxidase [377, 378]. However, the noradrenaline depletion produced by guanethidine is unlikely to result from inhibition of synthesis, since intra-cisternal injection of guanethidine does not prevent the accumulation of noradrenaline which follows brain monoamine oxidase inhibition, even though it does cause depletion of brain noradrenaline [323]. 

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

The translation of the correctly modified mature mRNA by the ribosome is also subject to regulation. The regulatory site of translation is mainly at the initiation of translation. Further regulatory elements include the availability of mRNA for ribosomal protein biosynthesis, as well as the concentration of mRNA. The availabihty of mRNA can be controlled by, for example, sequence-specific protein binding to the mRNA. The concentration of a specific mRNA is determined by a balance between its rate of synthesis (i.e. transcription) and its rate of degradation by RNases. The stabihty of a mRNA against nucleolytic degradation is thus a further factor that can determine the extent of biosynthesis of a protein. 

Compared to thermodynamically controlled synthesis, the initial rates of kinetically controlled synthesis are usually faster and the conversion can be complete. 

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