AMINO ACIDS: FUNDAMENTAL BIOMOLECULES TO METABOLIC REGULATORS AND THERAPEUTIC TARGETS IN HUMAN HEALTH AND DISEASE

Abstract

Amino acids are indispensable biological molecules that traditionally have been recognized as the fundamental building blocks of proteins. Contemporary research, however, has established that their biological functions extend considerably beyond protein synthesis. Amino acids participate in energy production, nitrogen homeostasis, redox regulation, neurotransmitter synthesis, immune responses, epigenetic regulation and intracellular signaling. Their metabolism is closely integrated with carbohydrate and lipid metabolism and contributes to the maintenance of cellular and systemic homeostasis. Deregulations of amino acid availability, transport and catabolism has increasingly been associated with metabolic, cardiovascular, renal, immune and malignant diseases. The present review provides an integrated overview of amino acid structure, classification, nutritional significance, digestion, absorption, transport and metabolic utilization, with particular emphasis on their emerging role as metabolic regulators. The review discusses essential, non-essential and conditionally essential amino acids, glucogenic and ketogenic amino acids, branched-chain amino acids (BCAAs), one-carbon metabolism, the urea cycle and amino-acid-dependent signaling pathways. Particular attention is given to glutamine, glutamate, arginine, methionine, glycine, serine, tryptophan and BCAAs because of their increasingly recognized roles in human disease. Recent evidence indicates that cancer cells undergo extensive amino acid metabolic reprogramming to support proliferation, biosynthesis, redox homeostasis and immune escape. Amino acid availability can influence tumor growth through nutrient-sensing pathways including mTOR signaling, while amino acid transporters and metabolic enzymes represent potential therapeutic targets. Similarly, altered BCAA metabolism has been associated with insulin resistance, diabetes and cardiovascular disease, although causal relationships may differ among individual amino acids and disease contexts. The kidney is also a major organ in amino acid synthesis, degradation, filtration, reabsorption and nitrogen handling, making amino acid metabolism particularly relevant to chronic and diabetic kidney diseases. Collectively, current evidence supports a transition from viewing amino acids merely as nutritional substrates toward understanding them as dynamic metabolic signals and potential biomarkers and therapeutic targets. Future research integrating metabolomics, stable-isotope tracing, multi-omics approaches and precision nutrition may help translate amino acid biology into personalized strategies for disease prevention and treatment.