Nucleic acid

“ As may be imagined, the primary difficulty was to prepare nucleic acids of such purity as admitted of their elementary chemical analysis. The necessary researches were to a large extent confined to two types of nucleic acid, one derived from yeast, and the other from the thymus gland; in other words, to representatives of the only two nucleic acids in nature, one derived from the nuclei of animal cells, the other from the nuclei of vegetable cells. ”

“ By simple hydrolysis with dilute mineral acids they are broken down into proteid, phosphoric acid, and one or more bodies known as nuclein bases. Of these latter substances, there are four well-defined bodies, viz., adenin, hypoxanthin, guanin, and xanthin, which from their peculiar chemical constitution are known as “purin bases.” In the body, there is present in many cells a peculiar intracellular enzyme termed nuclease, which has the power of liberating these purin bases from their combination as a component part of tissue nucleoproteids, or of the contained nucleic acid. ”

“ The nucleus, which in many cells is the largest and most central body, is of special importance. It contains a number of threadlike bodies, or chromosomes, that are the carriers of the cell’s heredity-controlling system. These contain granules of a material called chromatin, which is rich in a nucleic acid, DNA (deoxyribonucleic acid) . The chromosomes usually are not readily seen in the nucleus except when the cell, along with its nucleus, is dividing. When the nucleus is not dividing, a spherical body, the nucleolus, can be seen. (In some nuclei there may be more than one.) ”

“ Thus, from phosphatides, phosphoric acid is generated, and they could also be called phosphagens. Since 1926, however, the name phosphagens has been reserved for a group of organic substances that release their phosphoric acid very readily. The link between phosphorus and carbon is provided by oxygen in the phosphatides, by nitrogen in the phosphagens. In vertebrates, the basis for the phosphoric acid is creatine, whereas invertebrates have arginine instead.
Creatine Phosphate
Arginine phosphate Nuclein and Nucleic Acids
All parts of an organism are essential for life. ”

“ In the yeast cell the nucleus is represented by a homogeneous granule, probably of a nucleolar nature, surrounded and perhaps to some extent impregnated by chromatin and closely connected with a vacuole which often has chromatin at its periphery, and contains one or more volutin granules which appear to consist of nucleic acid in combination with an unknown base. Some observers consider that the yeast nucleus possesses a typical nuclear structure, and exhibits division by mitosis, but the evidence for this is not very satisfactory. ”

“ When a cell divides, the readily stainable bodies or chromosomes, present in definite number within the nucleus, are divided, usually by a most intricate process, in such a manner that equal amounts are bequeathed by the mother-cell to each of the two daughter-cells. Spencer favoured the view that the chromatin, which "consists of an organic acid (nucleic acid) rich in phosphorus, combined with an albuminous substance, probably a combination of various proteids" may be peculiarly unstable and active. ”

“ From later studies it seems probable that substances resembling the albumin of higher forms do not occur in bacteria, at least in appreciable quantities. Globulin has been reported by Hellmich in an undetermined bacterium, but is certainly not commonly found. The larger portion of the protein is of a comparatively simple type, in fact, consists of protamins most of which are in combination with nucleic acid as nucleoprotamins. ”

“ Under the influence of ATP, phosphoglyceric acid is synthesized and further built up by way of carbohydrate phosphates to hexose sugars and finally to starch. In many starchy fruits, a small proportion of phosphate remains attached to the end product.
The synthesis of proteins is under the control of deoxyribonucleic acid or ribonucleic acid, abbreviated by the symbols DNA and RNA. The genes in the nucleus are parts of a giant DNA molecule. RNA is a universal constituent of all living cells. Where protein synthesis is intense, the content in RNA is high. ”

“ We have mentioned previously that there are two main types of nucleic acids: DNA, the genetic material itself, and RNA, the molecule that translates the genetic message from DNA into terms the cell can use as “instructions” for making protein. Cells differ from each other on the basis of kinds of proteins they contain, and, since differences among cells determine differences among organisms, it follows that differences in the composition of DNA serve to explain the variety in living organisms populating the world. ”

“ It is not very fruitful to discuss whether proteins or nucleic acids are more important. That question is something like the one about the chicken and the egg. We cannot think of one without thinking of the other. ”

“ To accomplish this, we have chosen to describe three types of molecules that have become the basis of modern biology: deoxyribonucleic acid (DNA) , ribonucleic acid (RNA) , and proteins. We will show how radioactive isotopes can be used to pry into the innermost secrets of these substances. Before we can understand the function of these precious molecules, however, it will be necessary to review the structure of a cell and the physical nature of radioactive isotopes.
CELL THEORY: DNA IS THE SECRET OF LIFE
We have seen that all organisms are composed of essentially like parts, namely cells ”

“ The mitochondria have a central role in the reactions by which the energy of sugars is supplied for cellular activity. The importance of this vital activity is obvious. In this booklet, however, we are concerned with the processes, involving nucleic acids and proteins, that can be described as making up “the gene-action system”. The gene-action system is the series of biochemical events that regulate and direct all life processes by “transcription” of the genetic “information” contained in molecules of DNA.
10 RADIOACTIVE ISOTOPES: THE BIOLOGICAL DETECTIVES
Man ... ”

“ Because it has several important implications in biology and medicine, it is important to remember that DNA synthesis occurs only during the short, well-defined S period of the cell cycle. Other synthetic processes go on 40 throughout the cycle. We mentioned, for instance, that all cells can be labeled by a brief exposure to a radioactive amino acid, a precursor of proteins; this means that protein synthesis occurs throughout the entire cell cycle, including mitosis. When we use a radioactive RNA precursor, all cells except those in anaphase and metaphase are labeled ”

“ For example, if the enzyme were furnished with a mixture of 5 parts of A and 1 part of C, it would make strands containing, on the average, 25 sequences of AAA, 5 of AAC, 5 of ACA, 5 of CAA, and 1 each of ACC, CAC, and CCA. The proportion of triplets within the strands of a polynucleotide is reflected in the proportion of amino acids in polypeptides that are obtained in the cell-free system. Most of the present knowledge of the amino acid code is based on this concept. ”

“ It is assumed that the biogen molecules already present in living substance take out of the proteids of food certain groups of atoms, and dispose them so as to produce cyanogen-like compounds. The addition of oxygen atoms then brings the biogen molecule to the maximum of its power of decomposition, so that—partly spontaneously, but more especially when impelled by a stimulus—it breaks down somewhat explosively, causing the formation of carbonic acid. ”

“ But simple as the substance appears, composition is really very complicated. Professor Allman tells us that so difficult and wonderful is its chemistry, that in fact really very little is known about it. The best evidence we have, I believe, makes it tolerably certain that protoplasm consists of a combination of ammonia, carbonic acid, and water, and that every molecule of it is made up of 76 atoms, of which 36 are carbon, 26 hydrogen, 4 nitrogen, and 10 oxygen. ”

“ Since the nucleus of the cell is characterized in its structure by the presence of nucleo-proteins whose destruction results in the increased elimination of uric acid, it is not impossible that these nuclei are somewhat affected by the presence of alcohol in the body. ”

“ On the contrary, we live in the hope and in the faith that, by the advance of molecular physics, we shall by-and-by be able to see our way as clearly from the constituents of water to the properties of water, as we are now able to deduce the operations of a watch from the form of its parts and the manner in which they are put together. Is the case in any way changed when carbonic acid, water and ammonia disappear, and in their place, under the influence of preëxisting living protoplasm, an equivalent weight of the matter of life makes its appearance? ”

“ During life, when nutritive material is abundant, through the reversible action of certain enzymes, synthetic compounds are formed from the building stones furnished by the blood. These synthetic isomers cannot be hydrolyzed by the enzymes by which they are formed and hence on account of the isomeric structure are immune against destruc­tion. It is not impossible that the increase of the concentra­tion of acid in the cells after death trans­forms the isomers into that form in which they can be digested by the enzymes contained in the cell. ”

“ He reminds us that the oxidation and deaminisation of the nuclein derivatives, nucleins, nucleotides and nucleosides, is never complete. For purin bases and pyrimidin bases run side by side in the blood-stream together with uric acid. Also, that the unstable but soluble biurate is constantly changing into a less soluble type, viz., from one isomer to another. Moreover, since the red blood corpuscles abound in potassium, urates of potassium must also occur, and to these may be added, too, ammonium and calcium compounds in small quantities. ”

“ Artificial syntheses of amino-acids, by the action of ammonia upon glyoxylic acid and sorbic acid, both of which occur in plants and may be obtained by the oxidation of simple sugars, have been accomplished, and it seems probable that similar reactions in the plant protoplasm may give rise to the various amino-acids which unite together to form proteins. Nothing is known, however, of the process by which the more complicated closed-ring amino-acid compounds, such as proline, histidine, or tryptophane, are synthetized. ”

“ The outlines of the cells are for the most part distinctly marked in the specimens hardened in either chromic or picric acid, but more difficult to see in those prepared with osmic acid; their protoplasm is clear, and in the interior of each is an oval nucleus very large in proportion to the size of its cell. The long diameter of a typical nucleus is about 1/3000 inch, or about two-thirds of that of the cell.
The nuclei are granular, and very often contain several especially large and deeply stained granules ”

“ A compound of adenine, ribose, and phosphoric acid was found in yeast, blood, and in skeletal muscle of mammals. From 100 grams of such muscle, 0.35-0.40 grams of this compound were isolated. If the muscle is at rest, the compound contains three molecules of phosphoric acid, linked through oxygen atoms. ”

“ The carbon atom, for example, is prone to combine with other atoms in definite varied ways, and the high degree of complexity which the protein molecule possesses may depend in greater part upon the combining power of its carbon elements. The nitrogen atom makes the protein an extremely volatile compound, so that the latter burns readily in the tissue cells; and the hydrogen and oxygen bring their specific characteristics to the total molecule. ”

“ When examined under favorable conditions in its passive or resting state, the nucleus is seen to be bounded by a membrane which separates it from the cell plasm and gives it the characteristic sharp contour. It contains an apparently structureless nuclear substance, nucleoplasm or enchylema, in which are embedded one or more extremely minute particles called nucleoli, along with a network of exceedingly fine threads or fibers, which in the active living cell play an essential part in the production of new nuclei within the cell. ”

“ When cool and the particles have subsided, decant the hydrochloric and add nitric acid. The boiling must then be repeated until a drop of the liquid when placed under the microscope shows the valves or “frustules” clean. After allowing the diatoms to settle, the acid must be decanted, and pure water substituted. The washing must be repeated as in the former process until all the remains of crystals or acid are removed, when the specimens may be preserved in small phials as stated above. ”

“ In the DNA of higher organisms, there are only four types of nitrogen bases: adenine, guanine, thymine, and cytosine. Adenine in either strand of the helix pairs only with thymine in the opposite strand, and vice versa, and guanine pairs only with cytosine, and vice versa, so that 17 each strand is complementary in structure to the other strand (see Figure 12) . The full structure resembles a long twisted ladder, with the sugar and phosphate molecules of the nucleotides forming the uprights and the linked nitrogen bases forming the rungs. ”

“ This phenomenon of a double base in one acid, which had formerly been observed only in the nitro-muriatic acid, occurs continually in the vegetable kingdom, in which simple acid base, is very rarely found. Almost all the acids procurable from this kingdom have bases composed of charcoal and hydrogen, or of charcoal, hydrogen, and phosphorus, combined with more or less oxygen. All these bases, whether double or triple, are likewise formed into oxyds, having less oxygen than is necessary to give them the properties of acids. ”