Enzyme table

The term represents the kinetic efficiency of the enzyme. Table 14.4 lists turnover numbers for some representative enzymes. Catalase has the highest turnover number known each molecule of this enzyme can degrade 40 million molecules of HgOg in one second At the other end of the scale, lysozyme requires 2 seconds to cleave a glycosidic bond in its glycan substrate. 

Plasma also contains numerous other enzymes that perform no known physiologic function in blood. These apparently nonfunctional plasma enzymes arise from the routine normal destruction of erythrocytes, leukocytes, and other cells. Tissue damage or necrosis resulting from injury or disease is generally accompanied by increases in the levels of several nonfunctional plasma enzymes. Table 7-2 lists several enzymes used in diagnostic enzymology. 

The 6-chloromethyl substituent (series 5 and 6) is required for the inactivation of a-chymotrypsin. Nevertheless, there is only a transient inactivation of HLE and thrombin through the formation of a stable acyl-enzyme in spite of the presence of this group as demonstrated by the spontaneous or hydroxylamine-accelerated reactivation of the treated enzymes (Scheme 11.3, pathway b).21 HLE is specifically inhibited when such an alkylating function is absent (series 7), always through the formation of a transient acyl-enzyme (Table 11.2). 

The gem-dichloro and gem-dibromo analogues (24e and 24f) are more potent inhibitors of HLE compared to PPE, whereas the gem-difluoro (3-lactam 24a is equally efficient against the two enzymes (Table 11.4).34... 

A second area of drug discovery and development in which enzyme reactions play a critical role is in the study of drug metabolism and pharmacokinetics. The elimination of xenobiotics, including drug molecules, from systemic circulation is driven by metabolic transformations that are entirely catalyzed by enzymes. Table 1.2 lists some of the enzyme-catalyzed transformations of xenobiotics that commonly contribute to drug molecule elimination. These biotransformation reactions... 

They observed abrupt changes in the slope of Arrhenius plots for reactions catalyzed by NADH oxidase and p-lactate oxidase that correlate well with phase transitions detected by the ESR spectra of the nitroxide spin labels bound covalently to the enzymes (Table 5.4). 

Marker Enzymes Table 1 Useful in the Identification of Plant Organelles ... 

Hilvert s group used the same hapten [26] with a different spacer to generate an antibody catalyst which has very different thermodynamic parameters. It has a high entropy of activation but an enthalpy lower than that of the wild-type enzyme (Table 1, Antibody 1F7, Appendix entry 13.2a) (Hilvert et al., 1988 Hilvert and Nared, 1988). Wilson has determined an X-ray crystal structure for the Fab fragment of this antibody in a binary complex with its TSA (Haynes et al., 1994) which shows that amino acid residues in the active site of the antibody catalyst faithfully complement the components of the conformationally ordered transition state analogue (Fig. 11) while a trapped water molecule is probably responsible for the adverse entropy of activation. Thus it appears that antibodies have emulated enzymes in finding contrasting solutions to the same catalytic problem. 

GNG exploits the fact that most of the reactions of glycolysis are reversible so the enzymes are shared between the two pathways. There are three kinase reactions (glucokinase/hexokinase, PFK and pyruvate kinase), which are not physiologically reversible are therefore the problem steps in the synthesis of glucose these three steps are overcome using alternative enzymes (Table 6.5, see also Section 1.7.1). 

The data in Table 10.1 suggest that the reactivity of epoxide hydrolase toward alkene oxides is highly variable and appears to depend, among other things, on the size of the substrate (compare epoxybutane to epoxyoctane), steric features (compare epoxyoctane to cycloalkene oxides), and electronic factors (see the chlorinated epoxides). In fact, comprehensive structure-metabolism relationships have not been reported for substrates of EH, in contrast to some narrow relationships that are valid for closely related series of substrates. A group of arene oxides, along with two alkene oxides to be discussed below (epoxyoctane and styrene oxide), are compared as substrates of human liver EH in Table 10.2 [119]. Clearly, the two alkene oxides are among the better substrates for the human enzyme, as they are for the rat enzyme (Table 10.1). 

III.a.3.2. Enzyme inhibition. A number of drugs have the potential to inhibit microsomal enzymes (Table 6). Inhibition of drug metabolism may therefore result in exaggerated and prolonged responses, with an increased risk of toxicity. The onset of enzyme inhibition is usually more rapid than induction, occurring as soon as sufficient concentrations of the inhibitor appear in the liver. Thus for drugs... 

The drugs have variable potential for drug interactions via hepatic CYP450 enzymes (Table 5). Escitalopram has the lowest potential for interactions. 

There are many branches to the flavonoid biosynthetic pathways, with the best characterized being those leading to the colored anthocyanins and proanthocyanidins (PAs) and the generally colorless flavones, flavonols, and isoflavonoids. Genes or cDNAs have now been identified for all the core steps leading to anthocyanin, flavone, and flavonol formation, as well as many steps of the isoflavonoid branch, allowing extensive analysis of the encoded enzymes (Table 3.1). In addition, several DNA sequences are available for the modification enzymes that produce the variety of structures known within each class of compound. 

All the SSRIs have similar spectrums of efficacy and similar side-effect profiles. However, they are structurally and in some instances clinically distinct. For example, allergy to one SSRI does not predict allergy to another. Similarly, response or nonresponse to one SSRI does not necessarily predict a similar reaction to another medication in the class. SSRIs also have distinct pharmacokinetic properties, the most important of which are differences in half-life (Table 2-1) and the propensity to inhibit cytochrome P450 (CYP) enzymes (Table 1-1). 

Duloxetine is a moderate inhibitor of the CYP 2D6 enzyme and may increase the levels of other medications that use this enzyme (Table 1-1). Because of the risk of serotonin syndrome, duloxetine should not be combined with MAOIs. Because duloxetine is highly bound to plasma protein, combination with another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse events. 

As mentioned previously, beyond the unusually long half-life of fluoxetine and norfluoxetine, the other clinically meaningful distinction between the SSRIs is whether they produce substantial inhibition of specific CYP enzyme (Table 7-29). Fluvoxamine, fluoxetine, and paroxetine do, whereas citalopram and sertraline do not. As mentioned earlier, it is doubtful that the first three would be developed or approved for today s market because of their effects on CYP enzymes, which can cause serious and even fatal drug-drug interactions. 

Because of its substantial inhibition of CYP 3A3/4, this antidepressant is prone to pharmacokinetic drug-drug interactions with substrates for this enzyme ( Table 7-30). That is important because CYP 3A3/4 is responsible for approximately 50% of all known drug metabolism. Thus, there are a number of medications that either... 

The conversion of benzaldehyde by the encapsulated HNLs afforded mandelo-nitrile in 96-98% yield and 97-99% for all three enzymes. Free and entrapped HfoHNL catalyzed the conversion of hexanal with 94% , whereas ee-values of only 85 and 87% could be achieved with MeHNL and PaHNL preparations, respectively, limited by the intrinsic enantioselectivity of the enzymes (Table 9.4). Furthermore, the CLEAs from HfoHNL and PaHNL suffered from activity loss under the reaction conditions in contrast to MeHNL CLEA, indicating that the cross-linked aggregates from MeHNL are particularly robust and necessitate only traces of water to keep the catalytic activity [87]. 

Enzymes. The MFGM contains many enzymes (Table 3.12). These enzymes originate from the cytoplasm and membranes of the secretory cell and are present in the MFGM due to the mechanism of globule excretion from the cells. 

In addition to the enzymes described above, a number of other indigenous enzymes (Table 8.3) have been isolated and partially characterized (see Farkye, 1992). Although fairly high levels of some of these enzymes occur in milk, they have no apparent function in milk and will not be discussed further. 

Interpreting Vmax and Km Figure 6-12 shows a simple graphical method for obtaining an approximate value for Km. A more convenient procedure, using a doublereciprocal plot, is presented in Box 6-1. The Km can vary greatly from enzyme to enzyme, and even for different substrates of the same enzyme (Table 6-6). The term is sometimes used (often inappropriately) as an indicator of the affinity of an enzyme for its substrate. The actual meaning of Km depends on specific aspects of the reaction mechanism such as the number and relative rates of the individual steps. For reactions with two steps,... 

Biotin 515, 516,711, 721, 723 - 730,723s biosynthesis of 718, 745 in enzymes, table 724 mechanism of action 725 - 729 nutritional requirement 756 Biotin-binding proteins 728 Biotin carboxylase 724 Biotin carboxyl carrier protein 724 Biotin holoenzyme synthetase 724... 

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