Regulation, degradative pathways

Strains may be able to regulate the pathway of degradation of toluene to the availability of oxygen aerobic degradation by dioxygenation and under denitrifying conditions in the absence of oxygen by the benzylsuccinate pathway. 

Kiihner S, L Wohlbrand, I Fritz, W Wruck, C Hultschig, P Hufnagel, M Kube, R Reinhardt, R Rabus (2005) Substrate-dependent regulation of anaerobic degradation pathways for toluene and ethylbenzene in a denitrifying bacterium strain EbNl. J Bacteriol 187 1493-1503. 

It is very seldom that only a single substrate is present. It is therefore important to examine how the regulation of degradative pathways may be affected and, in particular, whether the simultaneous presence of other contaminants has an adverse effect. In addition, some of the components of a contaminant may directly inhibit degradation by toxification of the relevant organism. The example of azaarenes in groundwater at a wood preservation site that inhibit PAH degradation (Lantz et al. 1997) is noted in Chapter 14. 

Zinc protoporphyrin IX is a normal metabolite that is formed in trace amounts during haem biosynthesis. However, in iron deficiency or in impaired iron utilization, zinc becomes an alternative substrate for ferrochelatase and elevated levels of zinc protoporphyrin IX, which has a known low affinity for oxygen, are formed. This zinc-for-iron substitution is one of the first biochemical responses to iron depletion, and erythrocyte zinc protoporphyrin is therefore a very sensitive index of bone-marrow iron status (Labbe et ah, 1999). In addition, zinc protoporphyrin may regulate haem catabolism by acting as a competitive inhibitor of haem oxygenase, the key enzyme of the haem degradation pathway. However, it has been reported... 

Several steps in the intemalization/degradation pathway could be regulated by ubiquitination. In some cases, it is not the receptor, but another non-receptor protein that requires ubiquitination e.g. Epsl5, a protein that becomes receptor-associated, phosphorylated, ubiquitinated, and localized to the clathrin-coated pits upon ligand binding of the EGFR (Fazioli et al.. 

For the regulation of metabolic pathways metabolites are often used which are a product of that pathway. The basic strategy for the regulation is exemplified in the mechanisms employed in the biosynthetic and degradation pathways of amino acids, purines, pyrimidines, as well as in glycolysis. In most cases a metabolite (or similar molecule) of the pathway is utilized as the effector for the activation or inhibition of enzymes in that pathway. 

Of particular interest for regulatory processes are mechanisms by which the activity of growth regulating proteins and central transcription factors are controlled via ubiquiti-nylation. Often the cell uses signal pathway mediated protein phosphorylation in order to induce the regulated degradation of a signal protein. Examples are the G1 cychns, the tumor suppressor p53 and the inhibitor IxB. 

Microbial biosensors have been developed based on key hydrocarbon degradation pathways. These biosensors can be used as tools to examine the regulation of the degradation pathways. In addition to the use of empirically derived data from laboratory studies, a selective meta-analysis of published data from literature sources using catabolic hydrocarbon biosensors was conducted. The aim of this work was to demonstrate that biosensor specific QSARs may be developed to first assess the specificity of degradation pathways and then to assess the possibility of predicting analyte-specific degradation characteristics. 

Wang, Y., Rawlings, M., and Gibson, D.T., Identification of a membrane- protein and a truncated lysr-type regulator associated with the toluene degradation pathway in Pseudomonas putida FI, Molecular and Gen. Genet., 246, 570-579, 1995. 

Coleman, R.A., Lewin, T.M., Van Horn, C.G., Gonzalez-Baro, M.R. 2002. Do long-chain acyl-CoA synthetases regulate fatty acid entry into synthetic versus degradative pathways . / Nutr. 132, 2123-2126. 

W., Eds., The Proteosome-Ubiquitin Protein Degradation Pathway, Springer, Berlin, 2002 Saklatvala, J. and Nagase, H., Eds., Proteases and the Regulation of Biological Processes, Portland Press, London, 2003. 

Mayran, N., Parton, R.G. and Gmenberg, J. (2003) Annexin II regulates multivesicular endosome biogenesis in the degradation pathway of animal cells. Embo. J. 22, 3242-3253. 

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