ABSTRACT
Dysregulated metabolism has emerged as a critical mechanism in carcinogenesis. Reprogramming of metabolism contributes to tumor requirements for energetics, redox homeostasis and substrates for cell mass. Previous emphasis has centered on glucose metabolism, but recent discoveries have focused on the metabolism of nonessential amino acids (NEAA), e.g., glutamine, serine, aspartic acid, proline. The contributions of NEAA to tumor metabolism may be conceptualized as “parametabolic regulation.” In this context, proline, the only secondary proteinogenic amino (imino) acid has a special function. The proline metabolic system and the enzymes catalyzing synthesis and degradation are controlled by regulatory factors important in cancer, e.g., p53, PPAR-γ, AMPK, c-Myc, miRs, and which mediate redox signaling mechanisms for apoptosis, autophagy, redox homeostasis, and metabolic epigenetics.
