Extracellular export

However the synthesis of the polypeptide (typically a precursor pro-protein) is followed by various processes that can include targeting of polypeptides to specific organelles (e.g. mitochondria, ER, nucleus, vacuole or indeed for extracellular export), assistance with protein folding to form the proper tertiary structure, proteolytic processing (removing parts of the pro-protein) and further covalent modification (notably by glycosylation). Protein... 

Ancellin N, Colmont C, Su J, Li Q, Mittereder N, Chae SS, Stefansson S, Liau G, Hla T (2002) Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem 277 6667-6675... 

Exopolysaccharides, in almost every case, are synthesised at tire cell membrane and then exported from tire cell. The only exceptions that have been recorded to date are the homopolysaccharides levan and dextran which are synthesised extracellularly. 

As described above, because MAO is bound to mitochondrial outer membranes, MAOIs first increase the concentration of monoamines in the neuronal cytosol, followed by a secondary increase in the vesicle-bound transmitter. The enlarged vesicular pool will increase exocytotic release of transmitter, while an increase in cytoplasmic monoamines will both reduce carrier-mediated removal of transmitter from the synapse (because the favourable concentration gradient is reduced) and could even lead to net export of transmitter by the membrane transporter. That MAOIs increase the concentration of extracellular monoamines has been confirmed using intracranial microdialysis (Ferrer and Artigas 1994). 

Although a few mechanisms have so far been proposed to explain the antimicrobial properties exhibited by proanthocyanidins (e.g., inhibition of extracellular enzymes) [86], Jones et al. [83] postulated that their ability to bind bacterial cell coat polymers and their abihty to inhibit cell-associated proteolysis might be considered responsible for the observed activity (Table 1). Accordingly, despite the formation of complexes with cell coat polymers, proanthocyanidins penetrated to the cell wall in sufficient concentration to react with one or more ultra-structural components and to selectively inhibit cell wall synthesis. Decreased proteolysis in these strains may also reflect a reduction of the export of proteases from the cell in the presence of proanthocyanidins [83]. 

The vast bulk of proteins synthesized naturally by E. coli (i.e. its homologous proteins) are intracellular. Few are exported to the periplasmic space or released as true extracellular proteins. Heterologous proteins expressed in E. coli thus invariably accumulate in the cell cytoplasm. Intracellular protein production complicates downstream processing (relative to extracellular production) as ... 

Figure 7.4 Copper uptake and release in E. hirae. The extracellular reductase CorA reduces Cu2+ to Cu+ for uptake by CopA. In conditions of copper excess CopB functions as a copper exporter. (From Solioz and Stoyanov, 2003. Reproduced with permission from Blackwell Publishing Ltd.)...

Finally, we propose that APR becomes phosphorylated by the putative APR-kinase April and thereby inactivated, as a second resistance mechanism in addition to the 16S rRNA methylation by KamB, during biosynthesis or thereafter. Because AprZ is significantly similar to the StrK protein, a member of the protein family of extracellular alkaline phosphates and a STR-phosphate-specific dephosphorylase (see Section 2.2.1.2), this modification is urgently suggested by presence of the conserved aprZ gene in the biosynthetic cluster. April is a member of the large kinase family comprising all the antibiotic and protein kinases. As in the STR producers, the postulated APR-phosphate would exported via the ABC transport system AprV/AprW and set free by dephosphorylation outside the cells via the phospatase AprZ. 

In endocrine signaling the hormone is synthesized in specific signaling, or endocrine, cells and exported via exocytosis into the extracellular medium (e.g. blood or lymphatic fluid in animals). The hormone is then distributed throughout the entire body via the circulatory system so that remote regions of an organism can be reached. 

The metabolic control of methionine metabolism is complex and involves, for example, changes of enzyme levels in particular tissues, mechanisms linked to the kinetic properties of the various enzymes and their interaction with metabolic effectors [6, 7]. A particularly important metabolic effector is AdoMet. This inhibits the low Km isoenzymes of MAT, and MTHF reductase, inactivates betaine methyltransferase, but activates MAT III (the high-Km isoenzyme) and cystathionine /1-synthase. Therefore, high methionine intake and thus higher AdoMet levels favour trans-sulphuration, and when levels are low methionine is conserved. AdoHcy potently inhibits AdoMet-dependent methyltransferases and both Hey remethylating enzymes. Another important control mechanism is the export of Hey from cells into the extracellular space and plasma, which occurs as soon as intracellular levels increase [8]. 

Formation of Disulfide Cross-Links After folding into their native conformations, some proteins form intrachain or interchain disulfide bridges between Cys residues. In eukaryotes, disulfide bonds are common in proteins to be exported from cells. The cross-links formed in this way help to protect the native conformation of the protein molecule from denaturation in the extracellular environment, which can differ greatly from intracellular conditions and is generally oxidizing. 

The leader sequence of the Serratia marcescens extracellular nuclease has been removed and the gene for the resulting nontransportable protein cloned behind the leftward promoter (PL) of lambda (Ahrenholtz, Lorenz Wackernagel, 1994). In the presence of a temperature-sensitive repressor (cl857), the cells can be induced to produce this altered enzyme by an increase in temperature. This produces the nuclease within the cell and, because it cannot be exported, its intracellular concentrations rise, rapidly degrading the cellular genome. Limitations to this system are that cell survival is reduced to only 2 x 10 5. 

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