Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

Background. Sarcopenia, defined as the loss of skeletal muscle mass and function, is a major clinical problem in many chronic illnesses, in cancer and in the elderly. Exercise and adequate nutrition, peculiarly dependents on availability of essential amino acids, considered the primary strategies for prevention and treatment of protein synthetic deficits, affect both the efficient scavenging of aged and overused protein molecules and the renewal, by maintaining muscular protein synthesis. Many questions still remain about the regulation of protein syntheses and degradation. Degradation of inefficient proteins or organelles is performed by the sum of micro and macro-autophagy plus ubiquitin-proteasome system, activities known as proteostasis, necessary to preserve and promote protein masses and consequently, the body’s reserves. However, how protein synthesis is regulated, and how activation of the mTOR complex may modulate and transduce the flow of information provided by exercise and nutrition to balance proteostasis and syntheses, is far from being fully understood. We suggest that energy production and availability, thus also mitochondria, may have a pivotal role in synchronizing activity and functional outcomes of protein syntheses, and that those syntheses, since higly energy demanding, are main effectors of AMPK dependent autophagy activation by consuming ATP and producing AMP. Conclusion. While in normal conditions protein syntheses drive autophagy activation by decreasing ATP to AMP ratio, conversely autophagy may be inefficiently activated when chronic both low production and consumption of ATP would result in lowest concentrations of AMP, and therefore both blunted rates of protein syntheses and autophagy would be observed. We suggest that this functional hypothesis may explain sarcopenia in many pathological conditions , as in cancer or in aging muscles.

Chronic diseases are characterised by cell’s autophagy and proteins disarrangement resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia couses worse prognosis independentely of the principal disease. Currently, the cornerstone of therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of hematopoiesis. However, treatment strategies should incorporate the addition of heme, the principal biochemical constituent of haemoglobin. Heme synthesis follows a complex biochemical pathway. The limiting step of heme synthesis is D-ALA availability which, for its synthesis, requires Glycine and Succinil-CoA. Consequently, treatment of anaemia should not be based only on iron availability, but also on the availability of the molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate the standard iron infusion and the supply of essential amino acids and vitamins involved in the heme synthesis. We report preliminary data in selected elderly anaemic patients with congestive heart failure (CHF) and catabolic disarrangement, who, in addition to standard iron therapy, received personalized therapy with essential-AAs and vitamins involved in the maintenance of heme. Notably, such individualized therapy resulted in a significant increase in the serum concentration of haemoglobin after 30 days of treatment compared to standard iron therapy.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.