Characterization of mutant carnitine palmitoyltransferase I gene expressed in yeast and mice

Carnitine palmitoyltransferase I (CPTI) is the rate‑limiting enzyme in mitochondrial fatty acid β‑oxidation and is regulated by malonyl‑CoA. This dissertation investigates structural, regulatory, and physiological roles of CPTI using molecular and mouse models. Mutational analysis of the N‑ and C‑terminal domains of liver CPTI demonstrates compensatory and additive effects on malonyl‑CoA sensitivity, supporting interdomain regulatory interactions. In vivo studies using muscle CPTI knockout and transgenic mouse models reveal that CPTI is essential for development, regulates fatty acid metabolism during fasting, and influences body weight, lipid storage, and susceptibility to diabetes. These findings highlight CPTI as a key regulator of energy metabolism and a potential therapeutic target for metabolic disease.