Membrane metabolism, cell wall

The plasma membrane is a delicate, semipermeable, sheetlike covering for the entire cell. Forming an enclosure prevents gross loss of the intracellular contents the semipermeable character of the membrane permits the selective absorption of nutrients and the selective removal of metabolic waste products. In many plant and bacterial (but not animal) cells, a cell wall encompasses the plasma membrane. The cell wall is a more porous structure than the plasma membrane, but it is mechanically stronger because it is constructed of a covalently cross-linked, three-dimensional network. The cell wall maintains a cell s three-dimensional form when it is under stress. 

The biosynthesis and breakdown of fatty acids are both essential processes in cellular metabolism. Fatty acids are needed for critical structures such as cell membranes and cell walls, whereas fatty acid catabolism is a mechanism of energy generation in the cell. Although these metabolic pathways are present in all living... 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

From the above, it is clear that the gut wall represents more than just a physical barrier to oral drug absorption. In addition to the requirement to permeate the membrane of the enterocyte, the drug must avoid metabolism by the enzymes present in the gut wall cell as well as counter-absorptive efflux by transport proteins in the gut wall cell membrane. Metabolic enzymes expressed by the enterocyte include the cytochrome P450, glucuronyltransferases, sulfotransferases and esterases. The levels of expression of these enzymes in the small intestine can approach that of the liver. The most well-studied efflux transporter expressed by the enterocyte is P-gp. 

To use organic molecules as a food source, microorganisms have to be able to take up the substance and metabolize it within their cells. A prerequisite is that the molecules are water-soluble and that they are small enough to pass through the cell walls and membranes of the microorganism. Polymers are typically not water-soluble and, by definition, are not small molecules [4]. Therefore, the biodegradation of polymers typically needs to follow four distinct steps. 

Boron also appears to be involved in redox metabolism in cell membranes. Boron deficiency was shown to inhibit membrane H -ATPase isolated from plant roots, and H -ATPase-associated proton secretion is decreased in boron-deficient cell cultures [71]. Other studies show an effect of boron on membrane electron transport reactions and the stimulation of plasma reduced nicotinamide adenine dinucleotide (NADH) oxidase upon addition of boron to cell cultures [72, 73]. NADH oxidase in plasma membrane is believed to play a role in the reduction of ascorbate free radical to ascorbate [74]. One theory proposes that, by stimulating NADH oxidase to keep ascorbate reduced at the cell wall-membrane interface, the presence of boron is important in... 

Mechanism of Action A third-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Moderately absorbed from the G1 tract. Protein binding 60%-70%. Widely distributed. Not appreciably metabolized. Primarily excreted unchanged in urine. Minimally removed by hemodialysis. Half-life 1 -2 hr (increased in impaired renal function). 

Mechanism of Action A fixed-combination carbapenem. Imipenem penetrates the bacterial cell membrane and binds to penicillin-binding proteins, inhibiting cell wall synthesis. Cilastatin competitively inhibits the enzyme dehydropeptidase, preventing renal metabolism of imipenem. Therapeutic Effect Produces bacterial cell death. Pharmacokinetics Readily absorbed after IM administration. Protein binding 13%-21%. Widely distributed. Metabolized in the kidneys. Primarilyexcreted in urine. Removed by hemodialysis. Half-life 1 hr (increased in impaired renal function). 

Plants must be especially versatile in their handling of carbohydrates, for several reasons. First, plants are autotrophs, able to convert inorganic carbon (as C02) into organic compounds. Second, biosynthesis occurs primarily in plastids, membrane-bounded organelles unique to plants, and the movement of intermediates between cellular compartments is an important aspect of metabolism. Third, plants are not motile they cannot move to find better supplies of water, sunlight, or nutrients. They must have sufficient metabolic flexibility to allow them to adapt to changing conditions in the place where they are rooted. Finally, plants have thick cell walls made of carbohydrate polymers, which must be assembled outside the plasma membrane and which constitute a significant proportion of the cell s carbohydrate. 

There is thus some evidence for the tight binding of enzymes, especially glycosidases, to cell walls in both dicots and monocots. The nature and localization of these enzymes suggest that they may, perhaps, play a role in wall breakdown and such other processes as elongation growth. The membrane systems of plant cells are known to be involved in the transport, and introduction, of polysaccharides into the cell wall247-249 enzymes localized in the wall may also play a part in the metabolism of these polymers when they are transferred from the membrane system to the wall. 

There is at present no precise information concerning either the control mechanisms that govern wall-biogenesis or the interactions between wall biogenetic-processes and general cellular metabolism. The number of steps involved in the formation of a polysaccharide from a glycosyl-nucleotide is not known, and it is not clear how cellular control is extended beyond the plasma membrane, or how the cell wall is formed from the component polymers. Thus, it appears that the major questions posed by the problem of cell-wall biosynthesis have yet to be answered (see also, Ref. 217). 

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