Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Metabolism of Conjugated Proteins
Nucleic Acid Metabolism

This chapter discusses current views on the Biosynthesis AND DEGRADATION of prosthetic groups belonging to only two classes of complex Proteins: Nucleoproteins and Chromoproteins, whose protein components undergo transformations common to all proteins.

Nucleic Acids constitute an essential non-protein moiety of a complex Class of organic substances known as nucleoproteins (see Chapter 2), which form The basis of The Cell's hereditary apparatus, the Chromosomes. The protein components of nucleoproteins undergo diverse transformations analogous to the METABOLISM of proteins and their degradation products—Amino Acids—which are discussed in detail in Chapter 12. A vast body of factual material regarding nucleic acids, their Structure, and Functions in living organisms has been accumulated in recent years and is thoroughly reviewed in A number of specialized manuals and monographs. In addition to the unique role of nucleic acids in the storage and expression of hereditary information, their metabolic intermediates—specifically mono-, di-, and triphosphate nucleosides—perform crucial regulatory functions by controlling cellular Bioenergetics and The rate of metabolic processes. At the same time, nucleic acids are not essential dietary factors and do not play a significant role as an energy source. The following sections examine in detail (along with a Brief Overview of digestive processes) the metabolism of Nucleic Acids and their derivatives, specifically the pathways of biosynthesis and degradation of purine and pyrimidine NUCLEOTIDES, as well as Current Concepts of DNA and biogenesis and their role in Protein Synthesis.

The Digestion of nucleoproteins and the absorption of their degradation products take place in the digestive tract. Under the action of gastric Enzymes and, in part, Hydrochloric acid, dietary nucleoproteins are broken down into Polypeptides and nucleic acids; the former undergo hydrolytic Cleavage in the intestine to yield free amino acids. The breakdown of nucleic acids occurs in the Small Intestine, primarily via a hydrolytic pathway mediated by pancreatic juice DNase and RNase. The reaction products resulting from RNase action include purine and pyrimidine mononucleotides, a mixture of di- and trinucleotides, and RNase-resistant oligonucleotides. DNase action yields predominantly dinucleotides, oligonucleotides, and small amounts of mononucleotides. The complete Hydrolysis of nucleic acids down to the mononucleotide stage is presumably carried out by other, less well-characterized enzymes (phosphodiesterases) located in the intestinal mucosa.

Two hypotheses exist regarding the subsequent fate of mononucleotides. It is believed that in the intestine, mononucleotides are broken down to form nucleosides and phosphoric acid through the action of nonspecific Phosphatases (acid and alkaline) that hydrolyze the phosphoester bond of the mononucleotide (a "nucleotidase" action), and are absorbed in this form. According to the second hypothesis, mononucleotides are absorbed directly, and their breakdown occurs within the Cells of the intestinal mucosa. There is also evidence supporting the presence of nucleotidases in the intestinal wall that catalyze the hydrolytic cleavage of mononucleotides. Further breakdown of the resulting nucleosides inside mucosal cells proceeds predominantly via a phosphorolytic rather than a hydrolytic pathway*.

Nucleosides are absorbed primarily, and in this form, a portion of the nitrogenous bases can be utilized for the Synthesis of the body's own nucleic acids. If further degradation of nucleosides to free purine and pyrimidine bases occurs, guanine is not utilized for synthetic purposes. Other bases, as demonstrated by experiments using nitrogen-labeled adenine and uracil, can be incorporated into nucleic acids within Tissues. However, experimental data indicate that The biosynthesis of nitrogenous bases incorporated into the nucleic acids of Organs and tissues proceeds predominantly, if not entirely, de novo from low-molecular-weight nitrogenous and non-nitrogenous precursors.

Thus, the synthesis of nucleic acids, whose monomeric units are mononucleotides, is determined by the rate of Synthesis of purine and pyrimidine nucleotides; the synthesis of the latter, in turn, depends on the availability of all three constituent components. The source of ribose and deoxyribose is provided by glucose conversion products within The pentose phosphate cycle. To date, no evidence has been obtained regarding a significant role of dietary pentoses in nucleic acid synthesis. Phosphoric acid is also not a limiting factor, as it is supplied in sufficient quantities through the diet. Consequently, the Biosynthesis of Nucleic acids begins with the synthesis of nitrogenous bases (more precisely, monomeric molecules—mononucleotides).