Metabolism structural characteristics

Lewis DFV. Structural characteristics of human P450s involved in drug metabolism QSARs and lipophilicity profiles. Toxicology 2000 144 197-203. 

Molecular structure has been shown to influence absorption. By examining the structural characteristics of drugs that were in use, certain common characteristics of well-absorbed molecules were identified, commonly referred to as the rule of five. Some investigators have used this as a basis for characterizing the drug-likeness of a lead chemical. Other factors also come into play including receptor activity, metabolism profile and for CNS-active compounds, an ability to cross the blood-brain barrier. 

Immunocytochemical staining with antibody-gold probes is a powerful way to detect, localize, and quantify antigen molecules in tissue sections and cells (Figure 24.3). Metabolic processes can be followed, epitope mapping of the structural characteristics of macromolecules can be... 

Living systems are complex, ordered systems. This complexity and order is reflected in the molecules characteristic of life, in their interactions with each other, in the regulatory mechanisms that result from these interactions, and in the complex supramolecular structures characteristic of cells. Organization is also reflected in ordered metabolic and signaling pathways. Such complex, ordered structures and pathways are not characteristic of inanimate objects. 

Prior RL, Wu X. 2006. Anthocyanins Structural characteristics that result in unique metabolic patterns and biological activities. Free Rad Res 40 1014-1028. 

The list of examples detailed above is by no means exhaustive. Several additional examples of the structure-based control of translation, such as repressor protein binding sequences on the mRNA transcripts and ribozymes [39], are among others that could be listed. The intentions of this chapter are not to enumerate examples of how structural characteristics of mRNA influence its translation. What should be evident from the preceding discussion is that mRNA structure is a critical determinant of translation, and synthetic DNA technology offers the possibility to alter and probe the effects of mRNA sequence on its structure and the resulting translation efficiency. Further developments in this area will be immensely valuable to metabolic engineering as it will enable practitioners to fine-tune the fluxes of desired metabolic pathways through modulation of protein levels. 

Isozymes differ in structural characteristics but catalyze the same reaction. They provide a means of fine-tuning metabolism to meet the needs of a given tissue or developmental stage. The results of gene-duplication events provide the means for subtle regulation of enzyme function. 

Structural characteristics of unknown brassinosteroids in immature seed of P. vulgaris have been elucidated by GC/MS analyses. They are either stereoisomers of known brassinosteroids, or brassinosteroids that have been oxidized during metabolism [ 23-keto-brassinosteroids ( 34 ), brassinosteroids bearing either carbonyl (32 ) or hydroxyl ( 33 )], or brassinosteroids bearing an extra carbon atom [ CO ( 35 ) or COO ( 36 ) ] on the A ring ( Fig. 3 ). However, their complete structures remain to be characterized (30). 

More recently, Dearth and Hites (1991b) measured the half-lives of depuration of 14 different chlordane components (e.g., c/s- and /rans-chlordane and cis- and trans- nonachlor) and metabolites (e.g., heptachlor epoxide, oxychlordane) from the fat of rats fed chlordane in the diet for 28 days. Half-lives ranged from 5.92 days (c/s-chlordane) to 54.1 days (nonachlor III) and were apparently related to the metabolism rate of the various compounds. Structural characteristics associated with slowed depuration included an increasing number of chlorines on ring 1, the chlorine on Cl existing in an endo- (compared with an exo-) configuration, and the presence of two chlorines on C2. In mice treated once or every other day for 29 days, the whole body content of cis- and frans-chlordane remained at very low levels the content of cis- and frans-nonachlor and oxychlordane continued to increase with continued treatment (Hirasawa and Takizawa 1989). The investigators concluded that the chlordane isomers were readily metabolized, but that the nonachlor isomers were not. Oxychlordane, a metabolic intermediate of both chlordane isomers, is very slowly metabolized and tends to persist. 

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