Specific rate Product synthesis

Specific growth rate of the producing strain is also a relevant parameter for enzyme production by fermentation. Many enzymes are synthesized as growth-associated metabolites so that cell specific growth rate has a direct impact on enzyme specific rate of synthesis as shown by the non-structured model of Luedeking and Piret (1959) ... 

An acceleration of protein turnover by thyroxine also has been shown, implying that the hormone may alter various processes by a specific effect on synthesis of certain key proteins Involved in enzymatic reactions, Thus, not only does thyroxine increase the rate of formation of new protein material, hut it also may be responsible for the transformation of non-en/.ymalically active protein Into protein with enzymatic activity. The hormone has also been shown to be capable of acceleration of the synthesis of urea cycle enzymes and probably is essential for the production of a... 

Selection of mathematical equations able to represent the specific rates (for growth, product synthesis and substrate consumption) that can describe the phenomena identified in the previous steps. 

It is possible define the specific substrate consumption rate (Equation 7) and specific product synthesis rates (Equation 8) in a similar way to the specific growth rate. 

Similar to what was shown for growth, some models establish a linear relationship between the specific death rate (kj) and an autoinhibitory product synthesis (Lee et al., 1995). This autoinhibitory product is represented by the expression Xv/D, where Xv is a viable cells concentration, measured in terms of cell number per volume, and D is the specific feed rate that plays the part of substrate supply to the culture. By setting kj/px as a function of Xt/D (where Xt is a total cell concentration) it is possible to build up a more robust model that can fit a larger amount of experimental data (Equation 56) (Zeng et al., 1998). 

The products of the PI3-kinase reaction are different phosphoinositide derivatives phosphorylated at the 3 position, of which PtdIns(3,4,5)P3 has the greatest regulatory importance. PtIns(3,4,5)P3, like cAMP, has the function of a messenger substance that activates effector molecules in the sequence for further signal conduction. In contrast to cAMP, PtdIns(3,4,5)P3 is localized in the cell membrane and performs its function in close association with processes at the cell membrane. The concentration of PtdIns(3,4,5)P3 in the cell depends both on the rates of synthesis by PI3-kinases and the rates of hydrolysis of its phosphate residues. Several inositol polyphosphate phosphatases have been identified that remove the phosphates at position 3 or 5 of the inositol moiety. Among the inositol polyphosphate phosphatases with specificity for the 3-position, the PTEN phosphatase has been identified as a tumor supressor protein (see below). 

There are conflicting data on whether the availability of cholesterol and/or cholesteryl esters directly influences apo B secretion. Several studies have suggested that cholesterol supply can regulate VLDL secretion. For example, VLDL production in animals and man is decreased by statin treatment, and inhibition of cholesterol synthesis by a statin, an inhibitor of the rate-limiting step of cholesterol biosynthesis (Chapter 14), reduced VLDL secretion in perfused rat livers (M. Heimberg, 1990) and primary hepatocytes. However, this effect of statins can perhaps be ascribed to increased expression of LDL receptors rather than to a reduction in cholesterol synthesis (Section 7.1). Depletion of cholesterol in rodent hepatocytes by the ABCAl-dependent lipidation of apo A1 (Chapter 19) also decreases VLDL secretion (R. Lehner, 2004). Furthermore, the secretion of apo BlOO-containing VLDLs is increased in primary hepatocytes derived from Niemann-Pick Cl-deficient mice. Niemann-Pick Cl-deficiency causes a severe defect in trafficking of unesterified cholesterol out of the lysosomal/endosomal pathway and consequently, Niemann-Pick Cl-deficient hepatocytes accumulate 5- to 10-fold more unesterified cholesterol than do wild-type hepatocytes. In hepatocytes from Niemann-Pick Cl-deficient mice, cholesterol synthesis is increased and the rate of cholesterol esterification and the amount of the transcriptionally active form of SREBP-1 are also increased (J.E. Vance, 2007). However, because of multiple alterations in lipid metabolism in these hepatocytes, increased VLDL secretion cannot be attributed specifically to increased synthesis of cholesterol or cholesteryl esters. 

The reason for this is twofold, for not only is the number of initial states minimised, but the choice of rotational state for the product N2 molecule drops out also. It has been pointed out, rightly, [80.L1] that this is a considerable assumption reaction is considered to take place as a non-adiabatic transition between two electronic states of the N2O molecule, and although the ground state is linear, the other one is not consequently, the bending motions should play a part in the reaction process. Thus, whilst one may regard the numerical results of the simpler treatment with some circumspection, it remains an ideal vehicle for illustrating the state-to-state synthesis of specific rate functions. 

What is most urgently needed to solve these problems is an in-vitro system derived from a eukaryotic cell in which the addition of an inducer specifically enhances the rate of synthesis of a specific gene product. 

The specific incorporation rate (or the dilution of the precursor) gives the amount of product formed from the labeled precursor relative to that formed from the pool of endogenous precursor. Thus, for a specific incorporation rate of 0.1 % (or a dilution of 1 1,000), one product molecule in a thousand is formed from the isotopically labeled precursor. The specific incorporation rate is therefore dependent on the ratio of incorporation of endogenous to administered precursor molecules. It is influenced by the absolute rate of synthesis during the experiment only when this ratio is altered. It is easier to determine the specific activity of the product than its absolute amount since only a small portion of the product has to be isolated. 

Fig. 4. Productivity of the overall process of poly(3HB) synthesis as a function of specific rates of growth and poly(3HB) accumulation for final poly(3HB) contents of 40%, 60%, and 80%, corresponding to poly(3HB) concentrations of 33.3 g 1 , 75 g 1 , and 200 g 1, respectively. The initial and final poly(3HB)-free biomass concentrations are 0.1 g 1 and 50 g 1 , respectively...

In the previous discussion, extreme cases concerning the stage of product synthesis were considered, but actual production may occur in both exponential and stationary phases of growth. In order to account for this, the specific rate of product formation, qp, is then given by the Luedeking-Piret equation ... 

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