Cell, membrane wall biosynthesis

Many different glycosyltransferase activities involved in higher plant wall biosynthesis have been identified in cell free membrane fractions, but in only a few cases has glycosyltransferase activity been retained in detergent-solubilized preparations, and in even fewer cases have any purified polypeptides been identified as plant cell wall glycosyltransferases (29,33). 

As a result, the penicillin occupies the active site of the enzyme, and becomes bound via the active-site serine residue. This binding causes irreversible enzyme inhibition, and stops cell-wall biosynthesis. Growing cells are killed due to rupture of the cell membrane and loss of cellular contents. The binding reaction between penicillinbinding proteins and penicillins is chemically analogous to the action of P-lactamases (see Boxes 7.20 and 13.5) however, in the latter case, penicilloic acid is subsequently released from the P-lactamase, and the enzyme can continue to function. Inhibitors of acetylcholinesterase (see Box 7.26) also bind irreversibly to the enzyme through a serine hydroxyl. 

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

Pharmacology Vancomycin is a tricyclic glycopeptide antibiotic that inhibits cell-wall biosynthesis. It also alters bacterial-cell-membrane permeability and RNA synthesis. Pharmacokinetics ... 

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). 

Many of the proteins of membranes are enzymes. For example, the entire electron transport system of mitochondria (Chapter 18) is embedded in membranes and a number of highly lipid-soluble enzymes have been isolated. Examples are phosphatidylseiine decarboxylase, which converts phosphatidylserine to phosphatidylethanolamine in biosynthesis of the latter, and isoprenoid alcohol phosphokinase, which participates in bacterial cell wall synthesis (Chapter 20). A number of ectoenzymes are present predominantly on the outsides of cell membranes.329 Enzymes such as phospholipases (Chapter 12), which are present on membrane surfaces, often are relatively inactive when removed from the lipid environment but are active in the presence of phospholipid bilay-ers.330 33 The distribution of lipid chain lengths as well as the cholesterol content of the membrane can affect enzymatic activities.332... 

Further support comes from the studies relating cell wall biosynthesis and amino acid accumulation capacity in vitamin B6-deficient cells, since it is difficult to account for these observations without attributing considerable osmotic activity to the accumulated amino acids. Any description of accumulation which invokes amino acid attachment to intracellular binding sites, whose affinity can be reduced by a vitamin B6 deficiency, must account for the stimulation of uptake that accompanies the synthesis of essentially extracellular cell wall material. If the reduction in affinity occurs because the cell interior becomes overhydrated (a reasonable postulate which follows from the osmotic experiments), the beneficial effect of wall synthesis is not readily explicable, since vitamin B6-deficient cells have a swollen appearance which is not significantly altered after wall synthesis has been stimulated. Thus, the existing overhydration within the cell probably is not reversed by this change. In contrast, the deposition of additional wall substance would prevent further unfavorable consequences of swelling such as membrane distention, and, in this way, forestall the premature cessation of amino acid accumulation. 

The mechanism of toxicity for aminoglycosides has not been fully explained and is therefore unclear. It is known that the drug attaches to a bacterial cell wall and is drawn into the cell via channels made up of a protein, porin. Once inside the cell, the aminoglycoside attaches to the 30S bacterial ribosomes. Ribosomes are the intracellular structures responsible for manufacturing proteins. This attachment either inhibits protein biosynthesis or causes the cell to produce abnormal, ineffective proteins. The bacterial cell cannot survive with this impediment. This explanation, however, does not account for the potent bactericidal properties of these agents, since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not bactericidal. Recent experimental studies show that the initial site of action is the outer bacterial membrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer membrane probably accounts for most of the bactericidal activity. 

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... 

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