Substrate induction

Frazer, A. C., Ling, W. Young, L. Y. (1993). Substrate induction and metabolite accumulation during anaerobic toluene utilization by the denitrifying strain Tl. Applied and Environmental Microbiology, 59(9), 3157-60. 

The observed high degree of selectivity is a result of the fact that substrate induction and reagent induction reinforce each other and are thus intensified. This is therefore a case of double stereodifferentiation.70 The two compounds constitute what is known as a matched pair. In a mismatched pair the two inductive tendencies would be in competition, and selectivity would be reduced... 

Beginning with Nitowsky and Herz s observations of quantitative differences between established and recently isolated cell lines (K4) of diverse origins, demonstrations have been published of substrate induction (N23), of induction by osmolarity of the nutrient medium (N25), and of induction by adrenal glucocorticoids (C19, C20, N24). 

The reason for this pronounced species dependency does not appear to be solely related to species differences in the pharmacokinetics of the administered proliferator. Rather, species differences have been speculated to be related to differences in the concentration of an, as yet unidentified, specific cell receptor(s) and/or to an "initiating" metabolic perturbation such as depressed mitochondrial function resulting in substrate "overload" and subsequent substrate induction of peroxisome proliferation. 

Even [Rh(diene)L3]A salts were shown to be active, probably because alkene hydrogenation requires no more than three sites at the metal, two for hydrogen and one for the substrate. Induction periods are sometimes observed in these cases, no doubt because L(or cod) does not have to dissociate before H2 can add. Compared to the Wilkinson system, the side-reaction leading to isomerization of the alkene (e.g., 1-butene 2-butene) is a more serious competitor with hydrogenation itself. In applications requiring specific deuteration or where the isomerization product is nonhydrogenable, this can be a problem... 

T-2 toxin is believed to undergo selective C-4 deacetylation by hepatic microsomal carboxyesterase to yield HT-2 toxin (Ohta et al., 1977 Otta et al., 1978). Further metabolism by the same enzyme leads to the stepwise conversion of HT-2 toxin to the more polar metabolites 4-deactylneosolaniol and T-2 tetraol (Yoshizawa et al., 1980a). The lack of effect of T-2 toxin on the activity of heaptic esterase may be due to the non-specific nature of this enzyme. The low dose of toxin may not have been enough to cause substrate induction of the enzyme. The lack of effect of additives on the activity of hepatic esterase adds support to the concept that they do not alleviate T-2 toxicosis by promoting catabolism of the toxin. 

Substrate induction Here the substrate already contains a chiral center so that this creates uneven diastereotopic halves. The reaction proceeds via diasteromeric intermediates with different energies. The product resulting from the diastereo-meric intermediate with the lowest energy is IdneticaHy favored. 

Auxiliary induction Here the prochiral substrate is reacted first with a chiral auxiliary to form, basically, the starting point for a substrate induction. After the reaction the auxiliary is split-off, isolated, and can be re-used often. 

The remaining samples did not detect this activity, which may be related to the phenomenon of substrate induction. This phenomenon has been described for the amylolytic enzymes [10]. 

Smith (1962) has drawn an analogy between memory and substrate induction in microorganisms. He pointed out a number of common features in these two events. Particularly, a nerve impulse induces an increase in the activity of some enzyme systems (e.g., esterases). This is caused by the stimulation of secretion and synthesis. The mediators of these increases can serve as specific inductors which initiate the increase ojf enzyme biosynthesis. Such induction and the associated success of training can depend upon the amount of substrate. 

Substrate induction End product repression Repression by histones bb. Regulation of translation... 

Interplay between regulator genes, operator genes, and structural genes can lead to an activation of genes via substrate induction and to an inactivation of genes via end product repression. The decisive role falls to the repressors, the state of activity of which is controlled by low molecular weight metabolites, the so-called effectors. 

Fig. 149. Outline of substrate induction. A repressor Rep which is coded for by the regulator gene R blocks the operator gene O and, thus, the activity of all of the structural genes (Si - S3) of the operon (A). The repressor is inactivated by a low molecular weight effector E. E is the substrate of an enzyme which is encoded in the structural genes of the operon. After the inactivation of the repressor, the blocked operon becomes active and its structural genes code for proteins. Among the latter is the enzyme that can utilize the effector as substrate (B) (modified from Hess 1968).

At least the principles of substrate induction are realized in higher plants too. 

Substrate induction is subject to a temporal control of an unknown kind. Substrate induction anddi temporal control of substrate induction of a higher order have been discovered in a few further instances, such as different kinds of nitrate reductase and an enzyme involved in anthocyanin synthesis in Petunia hybrida. In addition, there is quite a number of enzymes for which substrate induction ora temporal control of synthesis of a higher order has been established. We shall become acquainted with examples of the latter type later. 

We shall not make a detailed analysis in this section of the extensive factual material in support of the validity of Jacob and Monod s concept of the structure and principles governing regulation of flie lactose operon. This material has recently been examined in many excellent surveys of problems associated with substrate induction of enzymes and the operon (Ames and Martin,... 

Under normal conditions the inductor is a diffusible substance or group of substances, metabolic products of the neighboring tissue. The closer the contact, the higher the concentration of these products. For this reason the reaction of the receptor systems has not developed very narrow specificity in the course of evolution. A reaction has developed to a signal, which could be an individual compound. However, this does not mean that other compounds cannot act as such signals. Under normal conditions other compounds simply are not present, and the receptor systems have not therefore developed very narrow specificity of reaction such as occurs during the allosteric interaction of specific proteins in the phenomena of substrate induction in bacteria (see Chapter 3). 

DeLapp and Fisher (7) showed marked elevation of the liver concentrations of hypoxanthine plus xanthine (H + X) and suggested that the mechanism of induction could involve substrate induction of enzyme synthesis. Stirpe and Della Corte (1) have shown that adenine induces an increase in the level of liver XDH. Woodward et al. (8) confirmed this observation and showed that the level of H + X was also elevated. It was shown that when adenine and allopurinol were fed together a 6-fold increase in activity could be obtained, with the tissue levels of H + X elevated to approximately 40 mgs per 100 gs tissue (allopurinol alone gave values of 15-20 mg % and controls were generally 1-4 mg %). It... 

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