Protein polysaccharides biosynthesis

D18. Derge, J. G., and Davidson, E. A., Protein-polysaccharide biosynthesis. Membrane-bound saccharides. Biochem. J. 126, 217-223 (1972). 

The metabolism of kerataii sulfate, both in vivo and in vitro in whole-cell systems, has been the subject of several investigations (see, e.g., Rod n, 1956d Davidson and Small, 1983a,b Conrad, 1968). However, the enzymic synthesis of this polysaccharide by acellular tissue preparations has not yet been achieved, and since the main emphasis of this review is on the mechanisms of cell-free protein polysaccharide biosynthesis, the present discussion will be limited largely to a few comments on the specific obstacles encountered in the study of this problem. 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

In a living cell, chains of biopolymers (DNA, RNA, proteins, polysaccharides) are built by special systems in an enzyme-mediated process called biosynthesis. This is a very robust process. Suffices it to say that if we fully stretch all DNA macromolecules synthesized in the human body during the life period the total length tm-ns out to be of astronomical scale two light-years And all the macromolecules forming this way are practically identical. 

It Is well known that Inorganic pyrophosphate (PP1) Is formed during biosynthesis of cellular constituents such as proteins, polysaccharides, nucleic acids and lipids. However, PP1 can also be formed by oxidative phosphorylation In mitochondria from different sources and by photophosphorylatlon In some phototrophs, such as Rhodospirill urn rubrum. 

Wzy-dependent pathway is most widespread in O polysaccharide biosynthesis. Following the assembly of O repeating units, the individual und-PP-linked O units are exported to the site of polymerization at the periplasmic face of the plasma membrane (Figure 2). This process requires a Wzx protein, the O unit transporter (flippase), which is highly hydrophobic with 12 potential transmembrane domains. Although the Wzx proteins share little primary sequence similarity, they do share structural features with bacterial permeases... 

The relevance of these considerations to the problems concerning the biosynthesis of protein polysaccharides is obvious. If, e.g., the problem of chain termination in the growth of polysaccharide chains is to be investigated, the isolation of an imdegraded product i.s required which contains only the end groups present in the native state. Also, a full understanding of the biosynthetic proce,sses requires more precise knowledge of the size of the primary products of synthesis in order to assess such problems as... 

Cellular aspects of protein polysaccharide synthesis, including intracellular sites of synthesis, mechanism of secretion, and regulation of polysaccharide biosynthesis in the intact cell. 

Early studies of the turnover of the chondroitin sulfate protein complex of rat costal cartilage (Gross ei al., I960) show-ed that the carbohydrate and protein moieties were metabolized at the same rate. Similarly, Campo and Dziewiatkowski (1962) found that the formation of both moieties proceeded in a roughly parallel fashion in cartilage preparations incubated in vitro. However, these experiments did not permit any conclusions as to the order in which the tw O components were synthesized. The investigations of the eell-frcc biosynthesis of the protein polysaccharide, reviewed above, have indicated that the synthesis of the protein core, or at least part of it, precedes the formation of the chondroitin sulfate chains and... 

Anabolism is the building up or biosynthesis, of complex molecules such as protein, nucleic adds and polysaccharides, from raw materials originating from intra- or extracellular sources. The biosyntheses are energy (ATP) requiring processes. 

In eukaryotes, anabolic and catabolic pathways that interconvert common products may take place in specific subcellular compartments. For example, many of the enzymes that degrade proteins and polysaccharides reside inside organelles called lysosomes. Similarly, fatty acid biosynthesis occurs in the cytosol, whereas fatty... 

An attractive hypothesis is the independent evolution in bacteria of their diffusible individualites and the currently recognized secondary metabolic pathways, in parallel with their surface components and their biosynthesis. An indicator for this would be the use of the same gene pool. The theory would include all substances that play a role in the build-up of glycan and other modified surface layers, lipids, murein, (glyco-) proteins (e.g., S-layers), polysaccharides, teichoic... 

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