Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Energy-requiring processes
Metabolism of nitrogen-containing compounds
Protein metabolism

In this chapter, breaking from the established pattern, we will examine both the nitrogen-compound transformation processes that yield energy and those that require an energy input. The rationale for this departure from the standard approach stems from the exceptionally close interdependence of metabolic processes involving nitrogen-containing molecules.

Cellular nitrogen compounds include Amino Acids and the Proteins they form, nitrogenous bases and their corresponding Nucleic Acids, most Cofactors, many Vitamins, and several other substances. Among these molecules, proteins are undoubtedly of paramount importance to the Organism, quantitatively prevailing over all other cellular macromolecules. Consequently, the nitrogen balance of an organism (or Cell) is dictated by Protein METABOLISM.

All Cells possess the capacity for Protein Synthesis. The Structure of protein molecules is unique to each species and is dictated by The sequence of nucleotide triplets in the sense strand of DNA (Chapter 3). It is precisely the Specificity of cellular proteins that determines the species specificity of living organisms. Therefore, when new cells are formed, protein molecules are synthesized de novo from low-molecular-weight precursors (amino acids). Protein Synthesis and degradation occur continuously even in mature cells, and a dynamic equilibrium is normally established between these two processes. Studies have shown, for example, that in the adult human body, 300–400 g of protein are degraded into amino acids daily, and roughly the same amount of amino acids is incorporated into newly formed protein molecules. Why is a metabolizing cell forced to synthesize protein constantly? Primarily because the half-life of many enzyme proteins is very short, ranging from 2 minutes to several days. The shortest-lived proteins are the Key Enzymes of metabolic pathways. Continuous protein degradation and synthesis allow cells to rapidly adjust enzyme levels and activity to meet metabolic demands. It has recently been discovered that the intracellular half-life of a protein is determined by The Nature of its N-terminal amino acid: if it readily binds to a specific protein (ubiquitin), the ubiquitin-tagged protein is swiftly attacked by proteinases and degraded. In contrast, structural proteins, Histones, Hemoglobin, and cytoskeletal proteins are exceptionally long-lived.

Protein degradation within cells occurs via Hydrolysis, which is most efficient in eukaryotes within Lysosomes and specialized Organelles known as proteasomes, though it also takes place to some extent in the Cytosol. Furthermore, cells capable of utilizing exogenous protein as a nutrient substrate typically possess extracellular (secretory) enzymes that drive the hydrolytic breakdown of protein outside The Cell. Protein Cleavage is catalyzed by peptide Hydrolases, which are subdivided into proteinases and peptidases. Proteinases (Endopeptidases) are capable of cleaving peptide bonds within the interior of the peptide chain. Exopeptidases attack the protein molecule from the chain ends: aminopeptidases from the N-terminus, and Carboxypeptidases from the C-terminus.

Thus, proteins in every cell are continuously broken down into amino acids. Amino acids cannot be stored within cells; they must be utilized immediately either in protein synthesis or through amino acid conversion pathways. Because the proportions of various amino acids in degrading and Newly synthesized proteins differ, a certain portion of the amino acids generated by Protein Hydrolysis does not participate in Biosynthesis. These amino acids primarily undergo deamination (removal of amino groups) and Transamination (exchange of keto and amino groups), as well as reactions involving their carboxyl and side chains.

Deamination reactions lead to the accumulation of amino nitrogen which, except for those amino groups that are re-incorporated into Amino acid biosynthesis, is excreted from the organism. The Mechanism of ammonia elimination in higher animals involves urea formation and is represented by The Urea Cycle. The breakdown of amino acid carbon skeletons involves their oxidation and ultimately yields a small number of products (typically 7) that can enter the TCA cycle or be utilized elsewhere, including contributing to the overall energy yield.

Amino acid synthesis can occur in the cells of all organisms, albeit to varying extents. For instance, autotrophic organisms (primarily plants), as well as many heterotrophic microorganisms, are capable of independently synthesizing all 20 Proteinogenic Amino Acids. At the same time, certain Representatives of the microbial world may require 10–18 amino acids for growth (polyauxotrophic strains of certain lactic acid Bacteria). The Human Body cannot synthesize 8 of the 20 protein amino acids; these Essential Amino Acids must be obtained through the diet.

The precursors for amino acid synthesis are intermediates of Catabolic pathways and the TCA cycle, as well as ammonium nitrogen. Alternatively, required Amino acids can be generated through interconversions (most frequently transamination) between keto acids and amino acids already present within the cell. If living nature relied solely on this second pathway, the planet's protein reserves would rapidly dwindle. It is nitrogen, forming the amino groups within protein molecules, that drives the continuous replenishment of protein resources while simultaneously acting as one of the primary limiting factors for organismal development. What are the sources of ammonium nitrogen that can be incorporated into amino acids? The answer to this question emerges from an examination of the global nitrogen cycle.