Protein and Nucleic Acid Biosynthesis

Inhibition of protein, RNA, and DNA synthesis by herbicides has been the subject of numerous reports and reviews (see, e.g.. Refs. 3, 4, and 137-139). Inhibition of the biosynthesis of any of these macromolecules would lead to an effective and abrupt cessation of plant growth. However, with very few exceptions, the reports on herbicidal interference with protein and nucleic acid synthesis reflect secondary effects resulting from an effect at a target site elsewhere in the cell. For example, any interruption of the production of metabolic energy, as a result of respiratory uncoupling and/or inhibition, would lead to a rapid cessation of macromolecular synthesis. In several surveys of herbicide effects on C-labeled precursor incorporation into protein and RNA in excised plant tissues and isolated mesophyll cells, dinitrophenols and hydroxybenzonitriles were the most potent inhibitors (Section 5.1 see, e.g.. Refs. 138 and 140). 

There are several examples of newly discovered herbicides being categorized as protein or nucleic acid inhibitors. In initial mode of action studies following discovery and commercialization, these processes have been identified as being the most sensitive with several herbicides whose 

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Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

In various fungi, including those of Basidiomycotina, numerous nucleoside-type metabolites and related free bases have been found (369). Apart from the typical components that are structural units of nucleic acid chains, like adenosine from Amanita muscaria (9), some of the nucleoside analogs apparently deserve special interest because of their biological and pharmaceutical activities, which eu-e usually induced by a slight difference in structural features. In addition, the role played by such nucleoside antibiotics in protein and nucleic acid biosynthesis might be of great importance. 

These target sites will include respiration, chlorophyll biosynthesis, isoprenoid biosynthesis, microtubule biosynthesis and function, cellulose biosynthesis, protein and nucleic acid biosynthesis, folic acid biosynthesis, and hormone biosynthesis and function. Only herbicides with proven direct activity on these target sites will be reviewed in this chapter. 

This great structural variety, however, complicates the specific biosynthesis of complex oligosaccharides. In general, the formation of each saccharide linkage requires specific enzymes ( one linkage—more than one enzyme ) and thus, in comparison with the enzymic synthesis of proteins and nucleic acids, much more effort is needed. 

A wide variety of other biochemical effects has been reported to be associated with treatment of cells with vinblastine, vincristine, and related compounds (S). These effects include inhibition of the biosynthesis of proteins and nucleic acids and of aspects of lipid metabolism it is not clear whether such effects contribute to the therapeutic or toxic actions of vincristine and vinblastine. Vinblastine and vincristine inhibit protein kinase C, an enzyme system that modulates cell growth and differentiation (9). The pharmacological significance of such inhibition has not been established, however, and it must be emphasized that the concentrations of the drugs required to inhibit protein kinase C are several orders of magnitude higher than those required to alter tubulin polymerization phenomena (10). 

Nucleotides play important roles in all major aspects of metabolism. ATP, an adenine nucleotide, is the major substance used by all organisms for the transfer of chemical energy from energy-yielding reactions to energy-requiring reactions such as biosynthesis. Other nucleotides are activated intermediates in the synthesis of carbohydrates, lipids, proteins, and nucleic acids. Adenine nucleotides are components of many major coenzymes, such as NAD+, NADP+, FAD, and CoA. (See chapter 10 for structures of these coenzymes.)... 

The fungicides inhibited protein and nucleic acid synthesis. RNA production was particularly affected. There was some evidence of a reduction in nuclear division. The primary effect of metalaxyl and furalaxyl probably involves impaired biosynthesis of RNA so that mitosis is inhibited (Kerkenaar, 1981 Fischer and Hayes, 1982). 

According to Ladonin and Spesivtsev (1974), maize tolerant to chloro-5-triazines stores the triazine taken up in the cytoplasm and in the sensitive pea it is stored in the nucleus, chloroplasts and mitochondria. They assume that the triazines are thus incorporated into proteins and nucleic acids as antimetabolites during the biosynthesis of internuclear nucleic acids. This may also be one of the explanations of the different sensitivity of plants to triazines. Black currant is also tolerant to 4 ppm simazine. According to Shone and Wood (1972) triazine translocated into the leaves of black currant cannot get from the tissue system into the mesophyll. The simazine taken up remains in the leaf veins and does not enter the chloroplasts. 

Carbohydrates are produced by the process of photosynthesis, which uses the energy of sunlight to produce hexoses from COj and HjO.The plants use these hexoses to harvest energy and produce ATP to fuel cellular function and to produce macromolecules, including starch, cellulose, fats, nucleic acids, and proteins. Animals depend on plants as a source of organic carbon. The hexoses are metabolized to generate ATP and are used as precursors for the biosynthesis of carbohydrates, fats, proteins, and nucleic acids. 

Methylation is an important reaction in the biosynthesis of endogenous compounds such as adrenaline and melatonin, in the inactivation of biogenic amines such as the catecholamines, serotonine and histamine, and in modulating the activities of macromolecules, such as proteins and nucleic acids. The number of xenobiotics that are methylated is comparatively modest, yet this reaction is seldom devoid of pharmacodynamic consequences (toxication or detoxication). Reactions of methylation imply the transfer of a methyl group from the onium-type cofactor S-adeno-sylmethionine (SAM) to the substrate by means of a methyltransferase. The activated methyl group from SAM is transferred to the acceptor molecules R — XH or RX, as shown in Fig. 31.30. 

It was suggested above that steroid hormones act by stimulating bioenergetic pathways, and that as a result of this stimulation, the biosynthesis of phospholipids, proteins, and nucleic acids is activated. After estrogen administration there is a rapid uptake of precursors P in phospholipids, glycine or other amino acids into proteins, and serine and formate into the purine and pyrimidines of the nucleic acid. 

In an anaboUc pathway, small precursor molecules are converted into complex molecules, including lipids, polysaccharides, proteins, and nucleic acids. Energy from ATP and NADH is necessary for these biosynthesis reactions to occur. Figure 3.4 illustrates that catabolism and anabolism occur simultaneously and that ATP and NADH serve as chemical "links" between the two processes. 

It can thus be concluded that flie chief problems concerned with the mechanism of biosynthesis of proteins and nucleic acids have now been solved. Analysis of this problem has now shifted to the level of filling in all the minor details (discovery of the nucleotide sequence of individual sRNA molecules, the terminal codons, heterogeneity of the aminoacyl-sRNA-synthetases, species specificity of these enzymes for sRNA and for other substrates). The solution of each major problem always brings forth a tremendous number of new problems, and creates a new branch of science. At the same time, however, it provides a decisive stimulus to the analysis of allied problems, sometimes even more important. 

Shapot, V. S., 1965, In Biosynthesis of Proteins and Nucleic Acids, ed. A, S. Spirin, Series Basis of Molecular Biology, Izd. Nauka, Moscow, p. 171. 

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