Cytoplasmic membrane porins

Decreased accumulation Reduced intracellular concentration of the drugs in the bacterial cell is linked to two mechanisms. One involves a decreased number of porin proteins in the outer membrane of the resistant cell, thereby impairing access of the drugs to the intracellular gyrase. The other mechanism is associated with an energy-dependent efflux system in the cytoplasmic membrane. 

In prokaryotes, the electron-driven proton pumps and ATP-synthesizing complex are located in the cytoplasmic membrane, the inner of two membranes. The outer membrane of bacteria, like that of mitochondria, is permeable to most small metabolites because of the presence of porins. 

MECHANISM OF ACTION AND RESISTANCE Tetracyclines inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNAto the acceptor (A) site on the mRNA-ribosome complex (Figure 46-1). They enter gram-negative bacteria by passive diffusion through channels formed by porins in the onter ceU membrane and by active transport that pumps tetracyclines across the cytoplasmic membrane. 

Figure 43-2. Beta-lactams and bacterial cell wall synthesis. The outer membrane shown in this simplified diagram is present only in gram-negative organisms. It is penetrated by proteins (porins) that are penrie-able to hydrophilic substances such as beta-lactam antibiotics. The peptidoglycan chains (mureins) are cross-linked by transpeptidases located in the cytoplasmic membrane, closely associated with penicillinbinding proteins (PBPs). Beta-lactam antibiotics bind to PBPs and inhibit transpeptidation, the final step in cell wall synthesis They also activate autolytic enzymes that cause lesions in the cell wall. Beta-lactamases, which inactivate beta-lactam antibiotics, may be present in the periplasmic space or on the outer surface of the cytoplasmic membrane. (Reproduced, with permission, from Katzung BG [editor]. Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

It is obvious that solvent tolerance is caused by a combination of the mechanisms described above. Figure 14.4.1.4 shows a schematic picture oftoluene penetration and efflux in the solvent tolerant strainP.putida S12. Toluene enters the cell through the outer membrane. At present, it is unclear whether toluene passes through porins or through the phospholipid part of the cell. The efflux pump recognizes and interacts with toluene in the cytoplasmic membrane. Toluene is then pumped into the extracellular medium. 

Both mitochondrial membranes are very rich in proteins. Porins (see p. 214) in the outer membrane allow small molecules (< 10 kDa) to be exchanged between the cytoplasm and the intermembrane space. By contrast, the inner mitochondrial membrane is completely impermeable even to small molecules (with the exception of O2, CO2, and H2O). Numerous transporters in the inner membrane ensure the import and export of important metabolites (see p. 212). The inner membrane also transports respiratory chain complexes, ATP synthase, and other enzymes. The matrix is also rich in enzymes (see B). 

VDAC plays a role in the regulated flux of metabolites—usually anionic species such as phosphate, chloride, organic anions, and the adenine nucleotides—across the outer membrane. VDAC appears to form an open p -barrel structure similar to that of the bacterial porins (Section 12.5.2). although mitochondrial porins and bacterial porins may have evolved independently. Some cytoplasmic kinases bind to VDAC, thereby obtaining preferential access to the exported ATP. In contrast, the inner membrane is intrinsically impermeable to nearly all ions and polar molecules. A large family of transporters shuttles metabolites such as ATP, pyruvate, and citrate across the inner mitochondrial membrane. The two faces of this membrane will be referred to as the matrix side and the cytosolic side (the latter because it is freely accessible to most small molecules in the cytosol). They are also called the N and P sides, respectively, because the membrane potential is negative on the matrix side and positive on the cytosolic side. 

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