Chapter 19: Oxidative Phosphorylation: The Respiratory Chain, ATP Synthesis, and Mitochondrial Genes

Section 19.1 introduces membrane receptors, particularly G protein–coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and ion channel–linked receptors. GPCRs are explained in the context of their interaction with heterotrimeric G proteins, the activation of adenylyl cyclase, and the generation of cyclic AMP (cAMP) as a second messenger. The roles of protein kinase A (PKA) and phosphodiesterases in regulating cAMP signaling are detailed, along with GTPase activity in G protein inactivation. Section 19.2 explores the phosphoinositide signaling pathway, including the activation of phospholipase C, production of IP₃ and DAG, release of intracellular Ca²⁺, and activation of protein kinase C (PKC). Calcium-binding proteins like calmodulin are highlighted for their role in mediating calcium-dependent effects. Section 19.3 focuses on receptor tyrosine kinases and the Ras/MAPK pathway, discussing autophosphorylation, SH2 domain interactions, and the signaling cascade involving Raf, MEK, and ERK that leads to changes in gene expression. Section 19.4 introduces other receptor systems such as guanylyl cyclases and insulin receptors, which regulate cellular metabolism through the PI3K/Akt pathway. The chapter also explores nuclear hormone receptors, which bind steroid hormones, thyroid hormones, and retinoids to directly regulate gene transcription in the nucleus. Section 19.5 addresses cross-talk between pathways and the importance of scaffolding proteins in ensuring signaling specificity. Section 19.6 discusses how dysregulation of these pathways leads to disease, especially cancer, and concludes with therapeutic strategies targeting kinases, receptors, and signaling intermediates. Overall, the chapter highlights the biochemical logic and precision that governs cellular decision-making in response to environmental cues.