Genetics of enzymatic dysfunctions in metabolic disorders and cancer

Abstract

Inherited metabolic disorders arise from mutations in genes involved in the biogenesis, assembly, or activity of metabolic enzymes, leading to enzymatic deficiency and severe metabolic impairments. Metabolic enzymes are essential for the normal functioning of cells and are involved in the production of amino acids, fatty acids and nucleotides, which are essential for cell growth, division and survival. When the activity of metabolic enzymes is disrupted due to mutations or changes in expression levels, it can result in various metabolic disorders that have also been linked to cancer development. However, there remains much to learn regarding the relationship between the dysregulation of metabolic enzymes and metabolic adaptations in cancer cells. In this review, we explore how dysregulated metabolism due to the alteration or change of metabolic enzymes in cancer cells plays a crucial role in tumor development, progression, metastasis and drug resistance. In addition, these changes in metabolism provide cancer cells with a number of advantages, including increased proliferation, resistance to apoptosis and the ability to evade the immune system. The tumor microenvironment, genetic context, and different signaling pathways further influence this interplay between cancer and metabolism. This review aims to explore how the dysregulation of metabolic enzymes in specific pathways, including the urea cycle, glycogen storage, lysosome storage, fatty acid oxidation, and mitochondrial respiration, contributes to the development of metabolic disorders and cancer. Additionally, the review seeks to shed light on why these enzymes represent crucial potential therapeutic targets and biomarkers in various cancer types.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery

“…The regulation of normal cell growth and unlimited tumor cell proliferation involves not only control of cell growth, but also apoptosis regulation ( 19 , 38 ). In disease-free individuals, STK1p levels are relatively low ( 18 ).…”

“…In disease-free individuals, STK1p levels are relatively low ( 18 ). In contrast, once multiple genetic mutations occur, resulting in enzyme deficiencies and metabolic disorders, including resistance to apoptosis and the ability to evade the immune system, unlimited growth occurs ( 18 , 38 ). Increased STK1p levels are reported to be correlated with clinical tumor stage I–III in patients with thyroid cancer ( 39 ).…”