Extracellular biosynthesis, regulation

Some less obvious phenomena of catecholamine transport and biosynthesis further illustrate the complexities of deciphering how efferents from midbrain dopamine neurons contribute to sleep-wake regulation. The plasma membrane norepinephrine transporter (NET), which is responsible for the uptake of extracellular noradrenaline, can also readily transport dopamine, and does so in vivo. This... 

Not all of the newly-synthesised PAF is released by neutrophils it is thought that release of PAF only occurs after a critical intracellular concentration has been reached even then, some PAF remains cell associated and does not act as a true extracellular effector molecule. The cell-associated PAF may thus play a role in cell-cell communication (e.g. neutrophil-neutrophil or neutrophil-endothelium interactions). Intra- and extracellular Ca2+ levels regulate both the biosynthesis and release of PAF. Increases in intracellular Ca2+ may allow PAF synthesis (but not release), whereas extracellular Ca2+ increases both synthesis and release in a dose-dependent manner. 

T. reesei is a useful experimental organism for studying regulation of extracellular protein biosynthesis. When grown in a medium in which an exogeneous inducer serves as the major or sole carbon source, T. reesei, synthesizes and secretes a cellololytic enzyme into the medium. Similarly, the extracellular cellulase is produced upon limitation of the carbon source and limitation of the utilization of the carbon source (31). Presently, there appears to be little data in the literature concerning regulation of cellulase biosynthesis. 

The specificity of blends of compounds used for pheromone communication by Lepidoptera species is the result of essentially two distinct sets of biosynthetic enzymes which regulate the production of specific olefinic bonds and synthesis of the oxygenated functional moiety, respectively. In Heliothis moths the regulatory systems that are responsible for production of the functional group during the final stages of pheromone biosynthesis consist of cellular acetate esterases and extracellular alcohol oxidases. Evidence indicates that the relative activities of these enzymes differ for each species of Heliothis. Thus, pheromone mediated reproductive isolation between closely related species of Heliothis is probably the result, in large measure, of the fact that some species require only aldehydes for communication while others use acetates, alcohols and aldehydes. 

Figure 1. Transcriptionally regulated network of exopolysaccharide galactoglucan biosynthesis in the Gram-negative soil bacterium S. meliloti that is affected by extracellular phosphate concentration and bacterial population density (AHL, N-acyl homoserine lactone HL, homoserine lactone).

The LDL receptor is a key component in the feedback-regulated maintenance of cholesterol homeostasis [1]. In fact, as an active interface between extracellular and intracellular cholesterol pools, it is itself subject to regulation at the cellular level (Fig. 2). LDL-derived cholesterol (generated by hydrolysis of LDL-bome cholesteryl esters) and its intracellularly generated oxidized derivatives mediate a complex series of feedback control mechanisms that protect the cell from over-accumulation of cholesterol. First, (oxy)sterols suppress the activities of key enzymes that determine the rate of cellular cholesterol biosynthesis. Second, the cholesterol activates the cytoplasmic enzyme acyl-CoA cholesterol acyltransferase, which allows the cells to store excess cholesterol in re-esterified form. Third, the synthesis of new LDL receptors is suppressed, preventing further cellular entry of LDL and thus cholesterol overloading. The coordinated regulation of LDL receptors and cholesterol synthetic enzymes relies on the sterol-modulated proteolysis of a membrane-bound transcription factor, SREBP, as described in Chapter 14. 

Aleksieva, P. and Micheva-Viteva, S. (2000) Regulation of extracellular acid phosphatase biosynthesis by phosphates in proteinase producing fungus Humicola lutea 120-5. Enzyme and Microbial Technology 27, 570-575. 

Coleman, Bown GS, Stormonth DA (1975) A model for the regulation of bacterial extracellular enzyme and toxin biosynthesis. J Theor Biol 52 143 -148... 

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