Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Processes Requiring Energy Input
Metabolism of Nitrogen-Containing Compounds
Protein Metabolism

In this chapter, breaking with the established pattern, we will examine both the transformation processes of nitrogen-containing compounds that lead to energy release and those that require an energy input. The rationale for this departure from convention stems from the very close interrelation between metabolic processes involving nitrogen-containing molecules.

Cellular nitrogen-containing compounds include Amino Acids and the Proteins formed from them, nitrogenous bases and the Nucleic Acids containing them, most Cofactors, many Vitamins, and several other substances. Among these molecules, proteins are undoubtedly of paramount importance to the Organism—quantitatively, they predominate over all other cellular macromolecules. Consequently, the nitrogen balance in an organism (Cell) is determined by Protein METABOLISM.

All Cells are capable of Protein Synthesis. The Structure of protein molecules is unique to each species and is determined by The sequence of nucleotide triplets in the DNA coding strand (Chapter 3). It is precisely the Specificity of cellular proteins that dictates the species specificity of 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 processes. Research has shown, for example, that in the adult human body, 300–400 g of protein are broken down into amino acids daily, and roughly the same amount of amino acids is incorporated into newly formed protein molecules. Why must a metabolizing cell constantly synthesize protein? 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 enable cells to rapidly adjust enzyme levels and activity to meet metabolic demands. It has recently been discovered that the half-life of a protein within a cell is determined by The Nature of its N-terminal amino acid: if it readily binds to a specific protein (ubiquitin), the ubiquitinated protein is rapidly attacked by proteinases and degraded. In contrast to enzymes, structural proteins, Histones, Hemoglobin, and cytoskeletal proteins are exceptionally long-lived.

Protein degradation in cells occurs via Hydrolysis, which in eukaryotes takes place most efficiently in Lysosomes and specialized Organelles known as proteasomes, though it also occurs partially in the Cytosol. Furthermore, cells capable of utilizing exogenous protein as a nutritional substrate typically possess extracellular (secretory) enzymes that carry out hydrolytic protein breakdown outside The Cell. Protein Cleavage is catalyzed by peptide Hydrolases, which are subdivided into proteinases and peptidases. Proteinases (Endopeptidases) can cleave peptide bonds within the peptide chain. Exopeptidases attack the peptide molecule from the ends of the chain: 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 immediately consumed either in protein synthesis or in amino acid transformation pathways. Because the proportions of various amino acids in degrading and Newly synthesized proteins differ, some of the amino acids generated by Protein Hydrolysis do 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 the modification of carboxyl and side groups.

During deamination reactions, amine nitrogen accumulates and, except for those amino groups that are re-incorporated into Amino acid biosynthesis, is excreted from the organism. The mechanism for excreting ammonia from higher animals is linked to urea formation and is represented by The Urea Cycle. The breakdown of amino acid carbon skeletons involves their oxidation and ultimately leads to The formation of a small number of products (usually 7) that can enter the TCA cycle or be utilized otherwise, including providing an energetic yield.

Amino acid synthesis can occur in the cells of all organisms, though 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 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 transformations (most frequently transamination) between keto acids and amino acids already present in the cell. If only this latter pathway operated in nature, the planet's protein reserves would rapidly deplete. It is precisely nitrogen, forming the amino groups within protein molecules, that drives the continuous replenishment of protein resources while serving 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 can be found by examining The Nitrogen Cycle in nature.