Negative transcriptional control

Figure 17-14 FNR regulation by redox in E. colt. The reduced form of FNR is functional as a transcription factor and contains a [4Fe-4S] cluster, exerting both positive and negative transcriptional control. Aerobic exposure results in oxidation to a [2Fe-2S] cluster and inactivation of FNR.

The results cited above indicate that there is no regulation of the synthesis of membrane proteins by the composition of the cell membrane. We know that the synthesis of some membrane proteins, such as the lac-transport protein in E. coli, is controlled at the level of transcription by the normal regulatory processes of the lac operon. The same type of control may apply for other membrane proteins as well. In other words, their synthesis is controlled by regulatory processes that are independent of the state of the membrane, but dependent upon other physiological parameters of the cell, such as positive and negative transcriptional controls, catabolite repression, the general level of energy metabolism and the availability of compounds necessary for protein synthesis. 

The well-investigated lactose operon of the bacterium Escherichial coli can be used here as an example of transcriptional control. The lac operon is a DNA sequence that is simultaneously subject to negative and positive control. The operon contains the structural genes for three proteins that are required for the utilization of lactose (one transporter and two enzymes), as well as control elements that serve to regulate the operon. 

Regulation is a blanket concept that covers all negative (i.e. stabilizing) feedback mechanisms of a product on its biosynthesis, such as inhibition of an enzyme by one of the downstream products or transcriptional control, which acts at the level of the gene. 

The major differences between prokaryotic and eukaryotic translation control mechanisms are related to the complexity of eukaryotic gene expression. Features that distinguish eukaryotic translation include mRNA export (spatial separation of transcription and translation), mRNA stability (the half-lives of mRNA can be modulated), negative translational control (the translation of certain mRNAs can be blocked by the binding of specific repressor proteins), initiation factor phosphorylation (mRNA translation rates are altered by certain circumstances when eIF-2 is phosphorylated), and translational frame-shifting (certain mRNAs can be frame-shifted so that a different polypeptide is synthesized). 

Figure 6. The biosynthetic pathway for the production of heme. The enzymes and metabolites are located in the mitochondria (M) and the cytosol (C). Heme negatively regulates ALA synthase at several points, three of which are shown in the figure. Exogenous ALA induces excess formation of heme precursors, including PpIX that can be utilized for photosensitization. (N) nucleus where transcriptional control occurs.

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