In this article we will discuss about:- 1. Formation of Nucleoproteins 2. Types of Nucleoprotein 3. Synthesis.
Formation of Nucleoproteins:
Nucleoproteins contain phosphoric acid and also other prosthetic group. Hence, they should be placed in a special class. Nucleoproteins are formed by the union of nucleic acid with basic protein. The nucleic acids, viz., deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are found both in animal and plant cells.
In the animal cells DNA is the chief nucleic acid-specially found in chromosome, whereas RNA is found in smaller quantity in the nucleus. RNA is also found in ribosomes (claude’s particles) inside the cytoplasm where they help in the synthesis of proteins. The breakdown and synthesis of RNA are continuously going on within the cell with the help of intracellular enzymes.
DNA is a stable compound and controls the hereditary characteristics of the cell. The nucleic acid is made up of many nucleotides (mononucleotide) making a double helical structure of two polynucleotide chains. Each mononucleotide is again composed of nucleoside and phosphoric acid.
Each nucleoside is composed of a pentose and a base as follows:
i. Pentose:
The pentose, ribose, is present in ribonucleic acid (RNA), whereas deoxyribose is present in deoxyribonucleic acid (DNA).
ii. Bases:
The bases are of two types:
a. Purine Bases:
Adenine and guanine (Fig. 10.103) are present in both the nucleic acids.
b. Pyrimidine Bases:
Cytosine and uracil are present in RNA, whereas cytosine along with thymine is present in DNA. In addition to DNA and RNA, nucleosides are also component of a number of coenzymes, like NAD and NADP and metabolically important compounds, such as ATP, UDPG, etc.
Since nucleoprotein is a composite product, its complete metabolism will mean the life history of all the component parts in it. The protein parts of the nucleoprotein molecules contain a high proportion of di-amino acids and undergo the same fate as the other proteins in the body.
The phosphoric acid part and the pentose molecule are treated by the body in the same way as the phosphates and carbohydrates derived from other sources. The special importance of the metabolism of nucleo proteins lies in the life history of its characteristic ingredients- the purine and the pyrimidine bases.
Types of Nucleoprotein:
Nucleoprotein metabolism may be of two types:
1. Exogenous, and
2. Endogenous.
1. Exogenous Nucleoprotein Metabolism:
Is undergone by the end products of nucleoprotein digestion, after they are absorbed. These end products are phosphoric acid, carbohydrate (pentose), the pyrimidine nucleosides (which are not further digested), the two purine bases (adenine and guanine) and probably some nucleotide.
2. Endogenous Nucleoprotein Metabolism:
Starts in a different way (Fig. 10.104). There are two kinds of tissue nucleotidases. The phosphonucleotidase splits off phosphoric acid and forms nucleosides. But the purine nucleotidase (more effective in slightly alkaline medium) takes away the purine bases, leaving phosphoric acid molecule combined with carbohydrate.
Taking everything together it will be seen that metabolism of purine may take place under two different conditions – first, when the purines remain combined as nucleosides and secondly, when they remain free as adenine and guanine.
The end product of purine metabolism is chiefly uric acid and slightly hypoxanthine and xanthine. But this is not all. All purine bases undergoing metabolic changes in the body, are not excreted in these forms. A good deal of it is lost in some unknown way. In dogs, excepting the Dalmatian variety, uric acid is further oxidised into allantoin and is excreted as such (Figs 10.103 & 10.105).
The intermediate metabolism of pyrimidine bases, e.g., cytosine, uracil and thymine is not clear. The catabolism of pyrimidines occurs mainly in the liver. Diets rich in thymine or DNA in rats produce increased excretion of β-aminoisobutyric acid. Based on fragmentary evidences obtained so far, the catabolic pathway of pyrimidines is shown in Fig. 10.106.
Feeding with pyrimidine bases increases the output of urea in the urine of dogs indicating the breakdown of the pyrimidine ring. Little is known about the fate of pentose. Probably they are oxidised.
The way by which purine bases undergo metabolic changes is briefly summarised in Fig. 10.105.
Functions of DNA and RNA:
In recent years it has been definitely established that genetic information from one cell to the daughter one is carried by DNA and different forms of RNA that help in protein synthesis.
A chromosome of the cell nucleus is composed of DNA, which is responsible for the passage of genetic code from one cell to the other. Just before mitosis the double helix of DNA separate from each other and with the help of an enzyme, DNA polymerase, a second chain exactly similar to the parent one is formed, thus giving it the original double helical structure.
The two similar double helixes go to the two daughter cells formed as a result of cell division giving them the same amount of DNA as the parent cell. In the process of meiosis such duplication of DNA in the parent cell does not take place and so the daughter cell contains half the number of original chromosomes.
Two types of RNA are also formed in the nucleus. One of them is single stranded messenger RNA (mRNA) which has a smaller molecule than DNA. Its synthesis is catalysed by the enzyme RNA polymerase. On being synthesised the mRNA comes out of the nucleus and becomes incorporated into the ribosomes of the cytoplasm.
The mRNA carries the genetic information to determine the sequence in which the amino acids are to be lined up in the polypeptide chain. In this process of synthesis, another type of RNA called soluble RNA (sRNA) or transfer RNA (tRNA) is also formed in the nucleus to participate in the process of synthesis. The tRNA attaches itself to the activated amino acids (amino acyl AMP) forming sRNA amino acid and carries them to the mRNA at the ribosomes.
The sRNA finds out the definite code word or codon on the mRNA, attaches to the specific amino acids and is set itself free to be used again. The long mRNA thread has a number of ribosomal structures known as polysomes (polyribosmoes, ergosomes) which are thus responsible for the syntheisis of many amino acids forming a polypeptide. Finally the mRNA is set free from the polypeptide chain of the completed protein and renews its help in protein synthesis.
RNA codes or codons for different amino acids are listed in Table 10.2.
Synthesis of Nucleoproteins:
Although in higher animals the power of protein synthesis is limited, yet nucleoproteins can certainly be synthesised in their bodies. A hen’s egg before incubation contains very little purine bases but after hatching the chick contains large amounts of nucleoproteins. Obviously, this must have been synthesised from other substances present in the egg.
In human infants the amount of nucleoprotein rapidly increases as growth advances, although, the chief food is milk which is almost free from nucleoproteins. From similar observations it has been definitely proved that the nucleoproteins can be synthesised in the body. Liver is the most probable site of nucleoprotein synthesis.
Nucleoproteins are compounds of simple basic proteins, protamines and histones with nucleic acid.
Nucleic acids are composed of:
(a) Phosphoric acid,
(b) A pentose, and
(c) A nitrogenous base – purine and pyrimidine.
Both the nitrogenous bases are synthesised in the body not as such but as their corresponding nucleotides.
Purine nucleotides are adenylic acid and guanylic acid (guanosine-5′-phosphate). These nucleotides are not formed directly. At first the nucleotide inosinic acid (hypoxanthine-ribose-5′-phosphate) is synthesised from the metabolic products of carbohydrate and protein. Different compounds of the purine ring are derived from formic acid, CO2, glutamine, aspartic acid, and glycine and have been shown in Fig. 10.112. The inosinic acid nucleotide, after being formed, is then converted into adenylic acid and guanilic acid.
Pyrimidine is also synthesised as nucleotides. Pyrimidine nucleotides are cytidylic acid, thymidylic acid and uridylic acid. The first step in the synthesis of pyrimidine nucleotide is the formation of orotic acid. It has been found by both vitro and vivo experiments that orotic acid is utilised for the synthesis of pyrimidine nucleotides.
Carbamylphosphate and aspartic acid take the initial role in the synthesis of pyrimidine nucleotide. In the pyrimidine ring, nitrogen at position 1 and carbon at position 2 are donated by carbamyl phosphate. Carbons at positions, 4, 5, 6 and nitrogen at position 3 of the pyrimidine ring are donated by aspartic acid (Fig. 10.113).