Biosynthesis of cell walls

Pharmacology Penicillins inhibit the biosynthesis of cell wall mucopeptide. They are bactericidal against sensitive organisms when adequate concentrations are reached and most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. 

The cell organellae in woody plants are the nucleus, mitochondrion, rough-endoplasmic reticulum (r-ER), smooth endoplasmic reticulum (s-ER), Golgi-body, plastid, vacuole, microbody, etc. Their functions are very complicated, and some have definite roles in the biosynthesis of cell-wall components. Hence, changes in size of cell organellae are likely to occur, since cell-wall composition depends upon the stage of wall development. 

Our electron microscopy observations have revealed some of the roles of cell organellae involved in biosynthesis of cell wall components (i) the plasma membrane is the site of cellulose synthesis. This supports the proposal that terminal and rosette complexes at the plasma membrane are responsible for cellulose synthesis, (ii) The Golgi-bodies and small circular vesicles derived from the r-ER s are involved in the biosynthesis and/or transport of the hemicelluloses. Our investigations, however, could not distinguish between what type of cell organellae contained what kind of hemicelluloses, and how these polymers were processed in the organellae. 

The biosynthesis of cell wall peptidoglycan, showing the sites of action of five antibiotics (shaded bars 1 = fosfomycin, 2 = cycloserine, 3 = bacitracin, 4 = vancomycin, 5 = 3-lactam antibiotics). Bactoprenol (BP) is the lipid membrane carrier that transports building blocks across the cytoplasmic membrane M, N-acetylmuramic acid Glc, glucose NAcGIc or G, /V-acetylglucosamine. 

M. A. Ghalambor and E. C. Heath, The biosynthesis of cell wall lipopolysaccharide in Escherichia coli, J. Biol. Chem. 241 3222 (1966). 

The poly (ribitol phosphate) synthetase and poly (glycerol phosphate) synthetase are inhibited by vancomycin, novobiocin, and Crystal Violet. Other antibiotic substances which interfere with cell-wall synthesis (such as bacitracin, ristocetin, and streptomycin) are almost without effect on the isolated synthetases, and penicillin is inhibitory at high concentrations only. Moreover, penicillin, vancomycin, and bacitracin do not markedly inhibit synthesis of cell-wall glycosaminopeptide in vitro, although the synthetical activity of extracts of cells which have been pretreated with these antibiotics is lowered.Convincing evidence that the primary site of inhibition by antibiotics is the biosynthesis of cell-wall material has been obtained only for the penicillins and cycloserine, and it appears that the action of even those antibiotics may be more complex than was originally supposed. 

JNakagawa, S Tamaki, S Tomioka, M Matsuhashi. Functional biosynthesis of cell wall peptidoglycan by polymorphic bifunctional polypeptides. J Biol Chem 259 13937-13946, 1984. 

Amino acid racemases are important for bacteria because they need D-alanine in the biosynthesis of cell walls. These enzymes require pyridoxal as the active cofactor. A racemization reaction starts with the aldimine complex between pyridoxal and an a-amino acid (Scheme 2.4). Deprotonation occurs at the a-carbon of amino acid, due to the electron-sink effect of pyridoxal. Reprotonation of the quinonoid intermediate at the opposite side provides the desired product (pathway a in Scheme 2.4). However, reprotonation may also take place at the C4 of pyridoxal (pathway b in Scheme 2.4). This kills the catalyst because one of its product, pyridoxamine, can no longer racemize an amino acid. 

In Volume 33 of this Series, we presented1 a review of the crystalline structures of polysaccharides published during the period 1967-1974. Detailed accounts of progress in structural studies on specific types of polysaccharides were presented in the Proceedings of the Twenty-sixth Symposium of the Colston Research Society and were subsequently published as a book.2 Precise methods for X-ray diffraction analysis of biopolymer structures were discussed by Hukins.3 The aspects of the structures of cellulose, mannan, and xylan, their organization in the cell wall, and the biosynthesis of cell-wall polysaccharides were described by Mackie.4 Work on the structures of the connective-tissue polysaccharides, O-acetylcellulose, and the various forms of amylose was reviewed by Atkins,5 Chanzy,6 and Sarko,7... 

Asamizu, T., and Nishi, A., 1979, Biosynthesis of cell-wall polysaccharides in cultured carrot cells. Planta 146 49-54. 

Thus far, the reasons for glycopeptide-resistance of S. aureus strains are not entirely clear. It is assumed that an increased biosynthesis of cell wall precursors combined with a thickened cell wall are the likely reasons.However, also the transferance of enterococcal resistance to S. aureus has been shown in the... 

Thus, though mycobacterial infections are difficult to treat under even the best of circumstances using currently available drugs, novel antibiotics targeting the biosynthesis of the unique mycobacterial cell wall structures show promise for clinical development. Further characterization of the enzymes involved in the biosynthesis of cell wall structures will facilitate the development of such antibiotics. Furthermore, studies of the cell wall biosynthetic pathways will likely uncover new potential targets for drug design efforts. 

Ericson, M.C. Elbein, A.D. In "Biosynthesis of cell wall polysaccharides and glycoproteins" Preiss, J, Ed. Academic Press ... 

In studies on the biosynthesis of cell-wall polysaccharides in cultured carrot cells, D-glucose was only incorporated into the neutral sugar residues, particularly cellulose, whereas myo-inositol appeared in the uronic acid and pentose residues. " An increase in cellulose content was observed during the thickening of the cell walls of parenchymous tissue of Discorea dumetorum tubers during storage. 

Biosynthesis of Cell Wall Polysaccharides and Glycoproteins Mary C. Ericson and Alan D. Elbein... 

Farkas, V. (1979). Biosynthesis of Cell Walls of Fungi . Microbiological Reviews, 43, 117-144. 

Experiments with penicillin show that resistant strains of staphylococci, even those that produce no penicillinase, take up no penicillin from solution, but susceptible strains of various species combine with from 200 to 750 molecules per cell. This amount is held tightly, cannot be washed away, and does not exchange with non-radioactive penicillin (Rowley et al., 1950 Maass and Johnson, 1949). The first molecules of penicillin are bound by inert material but, when this is saturated, the penicillin combines covalently with a receptor playing a key role in the biosynthesis of cell wall. Mammalian cells do not take up penicillin, but the bacterial cell binds it in less than 2 minutes. The penicillinbinding component is on the exterior, in the cytoplasmic membrane where the cell wall is synthesized. This component occurs in a phospholipid-containing fraction of staphylococci (Cooper, 1956). 

Some enzymatio reaotions that involve PLP include transaminations, which convert amino acids to ketones for use in the citric acid cycle and other pathways decarbox-yiation of amino acids for biosynthesis of neurotransmitters such as histamine, dopamine, and serotonin and inversion of amino acid chirality centers, such as required for the biosynthesis of cell walls in bacteria. 

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