Protein-Amino Acid Metabolism Disarrangements: The Hidden Enemy of Chronic Age-Related Conditions

Abstract

Proteins are macro-molecules crucial for cell life, which are made up of amino acids (AAs). In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation (i.e., inflammation), protein breakdown increases as the resulting AAs are consumed for metabolic proposes. Indeed, AAs are biochemical totipotent molecules which, when deaminated, can be transformed into energy, lipids, carbohydrates, and/or biochemical intermediates of fundamental cycles, such as the Krebs’ cycle. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement (HPD) is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD. Therefore, identification and treatment of proteins’ metabolic impairment with appropriate measurements and therapy is a clinical strategy that could improve the prognosis of patients with acute/chronic hypercatabolic inflammatory disease. Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement. We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment.

Discovery and characterization of a small‐molecule enteropeptidase inhibitor, SCO‐792

“…Amino acids show many functions within the body. For example, amino acids serve as the only source of nitrogen in mammals . Amino acid‐derived nitrogen is a critical element in the synthesis of the precursors (purine and/or pyrimidine) of major energy molecules, such as adenosine triphosphate, adenosine diphosphate, and/or nucleic acids .…”

“…For example, amino acids serve as the only source of nitrogen in mammals . Amino acid‐derived nitrogen is a critical element in the synthesis of the precursors (purine and/or pyrimidine) of major energy molecules, such as adenosine triphosphate, adenosine diphosphate, and/or nucleic acids . In addition, nitrogen is incorporated into compounds that can regulate major biochemical signaling pathways, such as nitric oxide .…”

Dietary Modifications of Nitrogen Intake Decreases Inflammation and Promotes Rejuvenation of Spleen in Aged Mice

“…Muscular proteins is a ready-to-use amino acid (AA) reservoir during fasting or stress. Therefore, inadequate protein dietary intake can easily impair protein balance and lead to muscle atrophy, impaired organ growth and/or functional decline, particularly in aged patients and/or with disease [17]. Thus, quantitative AA adequacy is pivotal for maintaining cell integrity in mammals.…”

Where the Pendulum of Knowledge Stands Now: Is Circulating Albumin a Marker of Inflammation or of Malnutrition? How to Manage Hypoalbuminemia by Nutrition?

“…In my opinion, one of the main points is the "measure", nitrogen balance based on urea syntheses, used to certify that any of those failures have been induced in spite of a most efficient nutritional approach. We have discussed elsewhere why urea synthesis is mostly dependent on arginine content of diets [5], [6] and discussed how arginine intake may influence both plasma and therefore urinary urea concentrations [7]. Thus, if nitrogen balance is used as the gold standard to certify sufficient quality of nitrogen intake, as we have observeded in animals [8] and paradoxically also in extreme human setting [9], [10] we may observe either a normalized nitrogen balance and the maintenance of clinical evidences of malnutrition comprehensive of unsuccessful treatment of hypoalbuminemia, unless we used very large doses of EAA as a major source of nitrogen.…”

“…On the contrary of NEAA, since EAA are the main promoters of protein syntheses and still antagonize cancer development in vitro [15], their sufficiently large availability condition evaluation of adequate nutritional supply [16] and only achieving a persistent success in normalizing liver syntheses of short lived circulating proteins (in progression of half life duration sequence: Retinol Binding Protein, Transthyretin/Prealbumin, Transferring) would be a necessary prelude to observe in time progression towards normality of albumin concentrations [17].…”