Chemistry and Biology of Proteins - F. Haurowitz 1953

Protein Synthesis
Nucleic Acids and Protein Synthesis

Nucleic Acids are present in all Cells of the Organism and are ascribed great significance in growth processes and the transmission of hereditary traits. Since both of these processes are closely linked to the synthesis of cellular Proteins, it is necessary to briefly review the localization of nucleic acids within cells and determine their relationship to cellular proteins. As for the question of the possible role of nucleic acids in Protein Synthesis, it will be discussed in the next section.

It was initially believed that nucleic acids were present exclusively in Cell nuclei and absent from the Cytoplasm; hence their name. Later, however, it was established that a significant portion of ribonucleic acid (see Chapter XI) is located in the cytoplasm. Unlike ribonucleic acid, deoxyribonucleic acid is found primarily in The Nucleus. Based on the old view that cell growth is determined solely by the nuclei, one would expect only deoxyribonucleic acid to participate in growth and protein synthesis. This, however, is completely contrary to reality. Experiments conducted in recent years have shown that Protein synthesis proceeds with particular intensity precisely in those PARTS OF THE cell that are richest in ribonucleic acid, i.e., in the nucleolus and cytoplasmic granules.

Despite the fact that the nucleolus constitutes only a small fraction of the nucleus in size, significant amounts of protein are apparently formed in or near it [61].

While the greater part of the Chromatin nucleus consists of euchromatin containing deoxyribonucleic acid, the nucleolar chromatin, called heterochromatin, contains primarily ribonucleic acid. The protein formed in the nucleolar region migrates toward the nuclear membrane, on the other side of which ribonucleotides and cytoplasmic proteins are synthesized [61]. Large amounts of ribonucleotides have been found in growing and secreting Organs, i.e., where METABOLISM/35.html">Protein Biosynthesis proceeds at an exceptionally high rate. In Organs of the adult organism that are slow-growing or completely non-growing, the ribonucleic acid content is very low, even if these organs are biologically very active [62].

Histochemical Methods capable of differentiating ribonucleotides from deoxyribonucleotides are based on treating cells with Ribonuclease. Prior to ribonuclease Treatment, the locations of both nucleic acids are identified using staining or Ultraviolet Microscopy. Following ribonuclease treatment, these same methods reveal only the deoxyribonucleic acid inaccessible to ribonuclease action within the cells [62].

Experiments carried out in recent years have shown that the turnover of ribonucleic acid occurs considerably faster than that of deoxyribonucleic acid. Two hours after an injection of radioactive phosphorus, 3.3% of Liver ribonucleotides contain P³²; during this same time interval, only 0.1% of deoxyribonucleotides manage to exchange their phosphorus for P³² [63]. Nucleic acids are also essential for tissue culture growth; the labile growth factor present in embryonic extracts and required for tissue culture growth is in all likelihood a nucleoprotein [64].

Nucleic acids contain numerous phosphoric acid residues, owing to which they possess distinctly pronounced acidic properties and can form salt-like compounds with proteins. The question of the formation and properties of artificial Nucleoproteins has already been discussed in Chapter XI. Due to their acidic properties, nucleic acids bind primarily with basic proteins, particularly Protamines and Histones. Both are found predominantly in nuclei, and it remains unclear whether they are also present in the cytoplasm. Of particular interest is the fact that nuclei contain either protamines or histones, but never both of these proteins simultaneously [65].

Protamines have been found in fish sperm cells, and histones in the nuclei of nucleated erythrocytes [66]. Compounds of these substances with nucleic acids are extracted from cells using a 1 M sodium chloride solution. Upon Dialysis of the resulting extracts, protamines diffuse through a semipermeable membrane, whereas nucleic acids remain inside the dialyzer [67]. In most cases, the Composition of Nucleic acid compounds with protamines and histones includes deoxyribonucleic acid. Ribonucleic acid was found in the fraction of the nucleus that is insoluble in a 1 M sodium chloride solution. This ribonucleic acid is bound not to protamines or histones, but to true proteins [68, 69].

Neither Nucleases nor Proteolytic Enzymes are capable of disrupting the Chromosome Structure on their own; however, this structure can be destroyed by the sequential action of nucleases and proteolytic enzymes on the Chromosomes [70].

Ribonucleic acid probably participates in protein synthesis processes, whereas deoxyribonucleic acid apparently determines cell Specificity to some extent. As already noted, the major part of deoxyribonucleic acid is located in the nucleus. Deoxyribonucleic acid constitutes the bulk of chromosomes. For example, calf Thymus chromosomes contain 90–92% deoxyribonucleic acid. In The Cell extract fraction that is insoluble in a 1 M sodium chloride solution, the deoxyribonucleic acid content is only 2–3% [68].

The deoxyribonucleic acid content in the sea urchin (Arbacia) egg increases 10–15 fold following Fertilization, while The amount of ribonucleic acid remains unchanged [71].

Deoxyribonucleic acid is considered an essential component of nuclear chromatin [72]. It is ascribed The Role of an agent capable of altering the type of pneumococci [74] and other Bacteria [75]. The action of deoxyribonucleic acid is also invoked to explain Changes in the enzymatic Properties of Individual Yeast strains occurring under The Influence of extracts added from other strains [76]. Deoxyribonucleic acid has been detected as a component of parametin—a toxic substance isolated from Paramecium aurelia [77]. It is also a constituent of the so-called structural Proteins of the cell, which exist within cells as elongated, thread-like particles insoluble in concentrated sodium chloride solutions, but soluble in alkaline urea solutions [78, 79].

Both in structural proteins and in chromosomes, nucleic acid molecules are oriented parallel to the protein fibrils [80] rather than perpendicular to their long axis, as previously assumed.

It is still unknown whether ribonucleic and Deoxyribonucleic Acids can convert into one another, although the possibility of such a process has been pointed out by many researchers [62].

Most researchers in the field of cytochemistry assign the role of the carrier of hereditary traits to the nuclear deoxyribonucleoprotein and view the positive Feulgen reaction (see Chapter XI) as proof of this substance's presence. This viewpoint is rejected by Stedman and Stedman [81], who explain the basophilic Properties of the Cell Nucleus by the presence of an acidic protein called chromosomin. Their argument is based on the fact that the red pigment formed by the action of the Feulgen reagent on deoxyribonucleic acid is Water-soluble, whereas the pigment produced by treating cell nuclei with the same reagent is either insoluble or adsorbed onto the nuclei. Furthermore, according to Stedman's data, chromosomes contain only 12–24% histone and 28–44% nucleic acid, whereas the content of chromosomin in them reaches 33–60%; the latter is a protein whose isoelectric point lies near pH 3–4. Stedman objects to the widespread view regarding the important role of nucleoprotamines and nucleohistones in the transmission of hereditary traits. In his opinion, The structure of protamines is so simple that these substances can hardly fulfill the role of carrier of hereditary properties ascribed to them. Consequently, Stedman believes that only a large protein molecule is capable of transmitting the complex mosaic of hereditary features. One must acknowledge these arguments as quite valid, just as one must recognize the soundness of the criticism directed against conventional views on the role of nucleoproteins in the transmission of heredity. However, it is difficult to imagine how a protein lacking deoxyribose could yield a positive Feulgen reaction. Resolving this issue requires further experimental work and broad Discussion of the obtained data.