BIOCHEMISTRY: A TEXTBOOK FOR MEDICAL UNIVERSITIES - E. S. Severin - 2004

SECTION 10. NUCLEOTIDE METABOLISM

Ribonucleoside and deoxyribonucleoside phosphates are vital components of living Cells.

✵ Nucleoside triphosphates (NTPs) serve as substrates for DNA and RNA Synthesis, which are essential for Protein Synthesis AND cellular proliferation.

✵ Evolution has selected the ADP-ATP cycle as the universal mechanism for coupling oxidation energy to biosynthetic processes. In certain biological pathways, other NTPs also function as Energy Sources.

✵ Nucleotide derivatives act as Donors of active substrates in the synthesis of homo- and Heteropolysaccharides, Lipids, and Proteins. For instance, UDP-glucose, UDP-galactose, GDP-mannose, UDP-N-acetylglucosamine, and CMP-acetylneuraminic acid participate in the synthesis of Glycogen and glycosaminoglycans, while CDP-Choline is involved in phospholipid synthesis.

✵ UDP-glucuronic acid, PAPS, and S-adenosylmethionine are key players in the universal detoxification system, which ensures the subsequent elimination of xenobiotics (foreign compounds) and certain endogenous metabolites from the body.

✵ AMP is an integral structural component of Coenzymes involved in dehydrogenation (NAD⁺, NADP⁺, FAD, FMN) and acylation (CoA).

✵ Cyclic nucleotide forms (cAMP, cGMP) mediate intracellular signal Transduction for Hormones, growth factors, Neurotransmitters, and other regulatory molecules.

Virtually all cells in the body are capable of synthesizing NUCLEOTIDES (with the exception of certain Blood Cells). Although Nucleic Acids from ingested food and the body's own Tissues can serve as alternative sources of these molecules, their contribution is strictly secondary and auxiliary.

The Structure AND NOMENCLATURE of nucleotides were covered in Section 4; this section will focus on the Metabolic pathways of these molecules in the body.

I. Digestion of Dietary Nucleic Acids in the Gastrointestinal Tract

Upon entering The Human Body, dietary Nucleoproteins undergo dissociation of their protein component in The Stomach and are denatured by the HCl of gastric juice (Fig. 10-1). Subsequently, the polynucleotide portion of these molecules is hydrolyzed in the intestine down to mononucleotides.

Class="center">Fig. 10-1. Digestion of dietary nucleic acids.

The breakdown of nucleic acids involves pancreatic juice DNases and RNases—endonucleases that hydrolyze macromolecules into oligonucleotides. These are further cleaved into a mixture of 3'- and 5'-mononucleotides by pancreatic phosphodiesterases. Nucleotidases and non-specific Phosphatases hydrolytically cleave the phosphate group from nucleotides, converting them into nucleosides. These nucleosides are either absorbed by small intestinal enterocytes or cleaved by intestinal nucleoside phosphorylases to yield ribose- or deoxyribose-1-phosphate, along with purine and pyrimidine bases.

Dietary Purines and Pyrimidines are not essential dietary factors and are utilized to a very limited extent for the synthesis of tissue nucleic acids. Enterocytes exhibit high activity of xanthine oxidase, an enzyme that converts the majority of internalized purines into uric acid, which is then excreted in the urine. Pyrimidine bases that fail to enter enterocytes are degraded by intestinal microflora into NH₃, CO₂, β-Alanine, and β-aminoisobutyrate.

Up to 90% of purine and Pyrimidine nucleotides are synthesized de novo from simple precursors in various body cells. Nitrogenous bases and nucleosides introduced into the bloodstream, as well as those generated through the intracellular Degradation of Nucleic acids, can be utilized in small amounts for nucleotide resynthesis via so-called Salvage Pathways.