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G6PD Deficiency and Oxidative Stress: Gene Function, Disease Mechanisms, and Clinically Relevant Variants

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What is G6PD? An Overview of the Gene, Enzyme, and Oxidative Stress Pathway Glucose-6-phosphate dehydrogenase (G6PD) is a critical metabolic enzyme encoded by the G6PD gene. It functions as the first and rate-limiting enzyme in the pentose phosphate pathway (PPP), a metabolic route that serves as a central hub for cellular antioxidant defense and nucleotide synthesis. G6PD catalyzes the oxidation of glucose-6-phosphate, generating two essential products: NADPH, the primary source of reducing power for cellular redox balance, and ribose-5-phosphate, a key precursor for nucleotide biosynthesis. NADPH is indispensable for regenerating reduced glutathione (GSH), which directly determines a cell’s ability to neutralize oxidative stress. Consequently, proper G6PD activity is essential for maintaining erythrocyte integrity and supports the unique metabolic demands of tumor cells. The G6PD gene is located on the X chromosome (Xq28). More than 230 point mutations have been identified, and appro...

How Lipoprotein Particles Shape Lipid Metabolism and Disease: From Cellular Response Mechanisms to CRISPR KO Models

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  When the metabolic balance of lipoprotein particles in the blood is disrupted, it triggers chronic inflammation—the common root of atherosclerosis, metabolic syndrome, and even neurodegenerative diseases. Circulating lipoprotein particles are the primary carriers of cholesterol and triglycerides: low-density lipoprotein (LDL) delivers cholesterol to tissues, while high-density lipoprotein (HDL) recycles it via reverse transport. Together, they maintain the delicate balance of lipid metabolism. When this balance is broken—such as through oxidative deposition of LDL or dysfunction of HDL—damage-associated molecular patterns (DAMPs) like oxidized phospholipids (OxPLs) activate innate immune signaling, driving foam cell formation and metabolic inflammation. Pathway enrichment analysis shows that lipoprotein response pathways are significantly enriched in functional genomics (FDR = 1.11×10⁻⁵), further confirming their role as key regulatory hubs. With CRISPR gene editing technology, i...