Representing metabolism

The third reaction of this cycle is the oxidation of the hydroxyl group at the /3-position to produce a /3-ketoacyl-CoA derivative. This second oxidation reaction is catalyzed by L-hydroxyacyl-CoA dehydrogenase, an enzyme that requires NAD as a coenzyme. NADH produced in this reaction represents metabolic energy. Each NADH produced in mitochondria by this reaction drives the synthesis of 2.5 molecules of ATP in the electron transport pathway. L-Hydroxyacyl-... 

Fig. 6 Seven-compartment PBPK model for deltamethrin Km represents metabolic rate constant (Kml carboxylesterase in blood, Km2 cytochrome P450 in liver, Km3 carboxylesterase in liver, KmFcc rate constant in feces) [49]...

Probably the most straightforward and well-known approach to metabolic modeling is to represent metabolic processes in terms of ordinary differential... 

Figure 1.1 Simple representation of a metabolic pathway. Compound B is the product of the first reaction and the substrate for the second reaction, and so on. Capital symbols represent metabolic intermediates and lower case letters with the suffix ase represent enzymes...

The student should be aware that a pathway is essentially a conceptual model developed by biochemists in order to represent the flow of compounds and energy through metabolism. Such models are simply ways of trying to explain experimental data. A potential problem in representing metabolic pathways as in Figure 1.1 is that there is an implication that they are physically and/or topographically organized sequences. This is not necessarily true. With some exceptions (described in Section 1.3), most enzymes are likely to be found free within the cytosol or a compartment of a cell where reactions occur when an enzyme and its substrate meet as a result of their own random motion. Clearly this would be very inefficient were it not for the fact that cells contain many copies of each enzyme and many molecules of each type of substrate. 

Metabolism Study The degradation of a protein to peptides and an amino acid moiety is commonly expected as a representative metabolic pattern. Therefore conventional biotransformation studies are not needed for biopharmaceuticals consisting of natural amino acids. However, metabolism studies of biopharmaceuticals containing nonnatural amino acid may provide useful information. In such cases radiolabeled proteins should be prepared to trace the pharmacokinetic behavior of the nonnatural amino acid fragments. 

Table 1 Some representative metabolic pathway databases...

Feedback regulation of the de novo pathway of purine biosynthesis. Solid lines represent metabolic pathways, and broken lines represent sites of feedback regulation. , Stimulatory effect , inhibitory effect. Regulatory enzymes A, PRPP synthetase B, amidophosphoribosyltransferase C, adenylosuccinate synthetase D, IMP dehydrogenase. 

Fast-moving bands of serum alkaline phosphatase essentially would represent metabolically altered intestinal alkaline phosphatase (analogous to the enzyme products in aging butanol extracts Fig. 21). 

Sorribas, A. Savageau, M. A, (1989c). Strategies for representing metabolic pathways within biochemical systems theory reversible pathways. Math. Biosci. 94,239-269. 

Figure 2 shows a representative metabolic route involved in the process of acrylic acid production and also the reaction rates (see Table 1). 

Additives that control bacterial growth may therefore exert both biostatic and biocidal effects. The mechanism of action responsible for each effect is not generally the same. Biostatic action is considered to represent metabolic inhibition which is released when the additive is removed. Biocidal activity causes irreversible damage to a vital structure or function of the cell. Dispersants may also be used to prevent attachment to a surface. 

There are several ways to graphically represent metabolic reactions wherein nodes represent the objects of interest and the links represent the relation between them. The nodes and links connecting them could represent one of the four following cases (Figure 11.9) ... 

Ciaccio (1910) studied the lipids in the chorionic villi of the placenta, but in his opinion the droplets represented metabolic byproducts rather than secretory antecedents. In 1912, Fellner demonstrated that placental extracts were capable of stimulating the uterus in the same way as ovarian extracts. It was not until 1921 that Fujimura suggested, from a careful cytological study of the placenta, that the lipid droplets constituted secretory granules. 

Most of the COj in the body is combined in the form of HCO3. Bicarbonate is a weak base and represents metabolic waste in the body. The level of HCO3 is... 

Studies to date on the endocrine regulation of G-6-Pase activity have raised many interesting questions. Do such changes in activity represent metabolic adaptation or do they represent hormonal regulation of the synthesis of a specific protein Here again the investigator meets with in-... 

Has diagnostic wliie ordy when it represents metabolism over the past lew hours. Sometimes, urine has been retained m the Madder so long that it represents an earlier meiabohc state. 

Figure 14.9 Representative metabolic pathways required for 3-HP production from glycerol in different species. The essential reactions are shown as arrows and rectangles dashed, the pathway that exists and is functional for 3-HP production in the host strain open, the pathway that does not exist or has not been reported yet in the host strain filled, pathway that has been introduced or overexpressed in the host strain. Enzymes that catalyze the target reactions are indicated in the black box with reaction number and strain designation, for example, glycerol dehydratase, K1 from K. pneumoniae or Lbl from L brevis. Strain designations are A, A. brasilense B, B. subtilis C, C butyricum Cn, C. necator ...

While the data shown here represents metabolic responses to changes in temperature, the method has general applicability to measurement of responses to many experimental variables, such as inhibitors, herbicides, and genetic alterations. It can be used to make rapid nondestructive measurements, repeatedly measure changes in a single sample, and examine reversibility of test parameters. Little or no sample preparation is required. 

A growth-process equation as a whole represents metabolism, and is the sum of the equations representing the other processes that take place concurrently. For the heterotrophic growth exhibited by yeasts, these latter can be regarded most simply as the processes of anabolism, which is cellular synthesis, and of catabolism, which provides the energy to bring about anabolism. A part of the substrate is utilized as... 

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