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.

Keywords: amino acids; catabolism; inflammation; muscle wasting; protein metabolism; sarcopenia.

Figure 1

Amino acid-derived intermediates fueling the tri-carboxilic acid cycle (TCA) (Kreb’s cycle). FFA = free fatty acids. Ala = alanine, Arg = arginine, Asa = aspartic acid, Asn = asparagine, Cys = cysteine, Gln = glutamine, Glu = glutamic acid, Gly = glycine, His = histidine, Ile = isoleucine, Leu = Leucine, Lys = lysine, Met = methionine, Phe = phenylalanine, Pro = proline, Ser = serine, Thr = threonine, Trp = tryptophan, Tyr = tyrosine, Val = valine.

Figure 2

Amino acids (AAs) as biochemical totipotent molecules.

Figure 3

The fate of amino acids (AAs) in muscle cell: physiologic (top) and hypercatabolic syndrome (HS) and/or insulin resistance (IS) (bottom). The increase in catabolic stimuli enhances protein breakdown and AA release in the blood stream. These AAs are used almost exclusively for energy production and gluconeogenesis, but not for de novo protein synthesis. This favors the onset and aggravation of muscle wasting.

Figure 4

Effects of protein disarrangements on various systems and electrolyte balance.