Intermediary Metabolism of Proteins and Recent Advances

Abstract

Protein metabolism is fundamental to human physiology, integrating dietary protein digestion and absorption, amino acid catabolism, nitrogen disposal, biosynthesis, regulatory signalling, and systemic adaptation. This review synthesizes foundational biochemical knowledge and recent advances to clarify the organization, regulation, clinical significance, and emerging applications of protein metabolism. It examines amino acid degradation and biosynthetic functions, tissue-specific metabolic processes, hormonal control, and nitrogen elimination, including vulnerabilities manifested in phenylketonuria, maple syrup urine disease, and urea cycle defects. Recent molecular research demonstrates that amino acids function not only as metabolic substrates but also as signalling molecules that influence gene expression, cellular growth, and immune function through regulatory pathways involving the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK). Proteomics and metabolomics have further enabled system-level characterization of protein turnover and metabolic flux, while CRISPR-based gene editing offers potential strategies for correcting inherited enzyme deficiencies. These developments have expanded the clinical relevance of protein metabolism to cancer, diabetes, sarcopenia, nutritional interventions, and personalized medicine. The integration of multi-omics data with systems biology, computational modelling, and network analysis may improve predictions of metabolic flux, pathway regulation, and therapeutic responses. This review concludes that protein metabolism constitutes a dynamic interface connecting biochemistry, physiology, disease mechanisms, and precision health. By integrating classical metabolic pathways with contemporary molecular and computational approaches, it provides a framework for understanding current biomedical applications and guiding future developments in disease prevention, diagnosis, and targeted therapy.